Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailab...Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailability.The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles(PLHNs)to enhance the oral absorption of BCS IV drugs.In this paper,taking paclitaxel(PTX)as a drug model,PTX-loaded PLHNs were prepared by a self-assembly method.Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability.Three P-gp inhibitors(D-α-tocopherol polyethylene glycol 1000 succinate,pluronic P123 and Solutol RHS15)were incorporated into selected PLHNs,and a CYP450 inhibitor(the extract of VBRB,BC0)was utilized to jointly promote the drug absorption.Properties of all the PLHNs were characterized systemically,including particle size,zeta potential,encapsulation efficiency,morphology,stability,in vitro drug release,mucoadhesion,in situ intestinal permeability and in vivo systemic exposure.It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested,with absolute bioavailability 21.95%.P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%,8-fold increase compared with that of PTX itself(4.75%).Taken together,our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption,especially for BCS IV drugs.展开更多
Atom transfer radical polymerization (ATRP) using cuprous chloride/2,2'-bipyridine (bipy) was applied to graft polymerization of styrene on the surface of silica nanoparticles to synthesize polymer-inorganic hybri...Atom transfer radical polymerization (ATRP) using cuprous chloride/2,2'-bipyridine (bipy) was applied to graft polymerization of styrene on the surface of silica nanoparticles to synthesize polymer-inorganic hybrid nanoparticles, 2-(4Chloromethylphenyl) ethyltriethoxysilane (CTES) was immobilized on the surface of silica nanoparticles through condensation reaction of the silanol groups on silica with triethoxysilane group of CTES. Then ATRP of St was initiated by this surface-modified silica nanoparticles bearing benzyl chloride groups, and formed PSt graft chains on the surface of silica nanoparticles. The thickness of the graft chains increased with reaction time. End group analysis confirmed the occurrence of ATRP. Thermal analysis indicated that thermal stabilization of these resulting hybrid nanoparticles also increases with polymerization conversion. The results above show that this 'grafting from' reaction could be used for the preparation of polymer-inorganic hybrid nanoparticles with controlled structure of the polymer's end groups.展开更多
Particulate carriers such as polymeric micelles (PMs) and liposomes have been investigated to increase drug accumulation in tumors and reduce distribution to healthy tissues. In this study, we prepared PM and hybrid n...Particulate carriers such as polymeric micelles (PMs) and liposomes have been investigated to increase drug accumulation in tumors and reduce distribution to healthy tissues. In this study, we prepared PM and hybrid nanoparticles (HNPs) with poly(ethylene oxide)-block-poly(methacrylic acid) (PEO-b-PMAA) for loading cisplatin, and evaluated cisplatin release, cytotoxicity, and biodistribution in mice. PM composed of PEO-b-PMAA and HNPs composed of egg phosphatidylcholine (EPC)/PEO-b-PMAA at molar ratios of 50/2.8 (HNP-P5) and 50/50 (HNP-P50), respectively, were prepared by a nanoprecipitation method. The sizes of PM, HNP-P5, and HNP-P50 after inclusion of cisplatin were approximately 200, 100, and 55 nm, respectively, and their entrapment efficiencies were approximately 44% - 66%. In the drug-release study, HNP-P5 and HNP-P50 showed reduced release of cisplatin compared with PM. Regarding the cytotoxic assay, HNP-P5 exhibited lower cytotoxicity for mouse Lewis lung carcinoma (LLC) and mouse colon carcinoma Colon 26 cells than PM and HNP-P50. In terms of biodistribution, PM could significantly improve blood circulation and tumor accumulation after intravenous injection into Colon 26 tumor-bearing mice compared with free cisplatin, but HNP-P5 and HNP-P50 did not. EPC in HNPs might be destabilized in the circulation, although it could reduce release of cisplatin in in vitro experiments. This study suggested that polymeric micelles composed of PEO-b-PMAA are a better carrier for cisplatin than hybrid nanoparticles composed of PEO-b-PMAA and EPC.展开更多
The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important r...The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.展开更多
Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of t...Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody.Here,a molecular engineering technique was used for sitespecific conjugation of antibodies to nanoparticles.We designed an anti-claudin 3(CLDN3)antibody containing a single cysteine residue,h4 G3 cys,then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles(LPNs).Because of their negatively charged lipid coating,LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4 G3 cys.The activity of h4 G3 cys was tested by measuring the binding of h4 G3 cys-conjugated LPNs(C-LPNs)to CLDN3-positive tumor cells and assessing its subsequent photothermal effects.C-LPNsspecifically recognized CLDN3-overexpressing T47 D breast cancer cells but not CLDN3-negative Hs578 T breast cancer cells.High binding of C-LPNs to CLDN3-overexpressing T47 D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy.Consistent with this,intravenous injection of C-LPNsin a T47 D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases.Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.展开更多
Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceuticalpreparations such as controlled release formulations, parenteral preparations, surgicaltreatment application...Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceuticalpreparations such as controlled release formulations, parenteral preparations, surgicaltreatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticlesfor topical and site targeting delivery of Norfloxacin by emulsification solvent evaporationmethod (ESE). The design of experiment (DOE) was done by using software to optimize the result, andthen a surface plot was generated to compare with the practical results. The surface morphology, particlesize, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized bySEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterizedby DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited anaverage particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution withpolydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymerhybrid nanoparticles were confirmed by zeta potential, showed the value from t23.4 ± 1.5 mVto t41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonasaeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these two.Lipid-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in24 h. A stability study of the optimized formulation showed the suitable condition for the storage oflipid-polymer hybrid nanoparticles was at 4 ± 2 C/60 ± 5% RH. These results illustrated high potential oflipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.展开更多
A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)-co-(2-(D-galactose)methylmethacryl-ate)](P(MACPTS-co-MAG...A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)-co-(2-(D-galactose)methylmethacryl-ate)](P(MACPTS-co-MAGP)) and AgNPs is developed to deliver the anti-cancer drug camptothecin(CPT) and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer sidechains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence( "off" state) due to the nanoparticle surface energy transfer(NSET) effect.Upon the exposure to glutathione(GSH), the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT("on" state). The system offers a platform to track the CPT delivery and releasing in real time展开更多
Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This s...Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This study developed bifunctional oral lipid polymer hybrid nanoparticles(R8-PEG-PPNPs)that deliver superoxide dismutase(SOD)for the treatment of ulcerative colitis(UC).R8-PEG-PPNPs was composed of PCADK,PLGA,lecithin,and co-modified with stearic acid-octa-arginine and polyethylene glycol.The nanoparticles(NPs)are uniformly dispersed with a complete spherical structure.In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection.In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000µg/mL and promote cellular uptake.In experiments with ulcerative colitis mice,R8-PEG-PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation.Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs.展开更多
The gelation of crude oil with high wax and asphaltene content at low temperatures often results in the block of transportation pipeline in Africa. In recent years, it was reported that surface hydrophobicmodified nan...The gelation of crude oil with high wax and asphaltene content at low temperatures often results in the block of transportation pipeline in Africa. In recent years, it was reported that surface hydrophobicmodified nanoparticles have important applications in crude oil flow modification. In this work, four kinds of core-shell hybride nanoparticles by grafting poly(octadecyl, docosyl acrylate) and poly(acrylate-α-olefin) onto the surface of nano-sized SiO_(2) were synthesized by grafting polymerization method.The chemical structure of nanoparticles was analyzed by Fourier transform infrared spectroscopy(FT-IR),scanning electron microscopy(SEM) and thermogravimetric analysis(TGA). The rheological behaviors of crude oil and precipitation of asphaltenes in the presence of nanoparticles were studied by measuring the viscose-temperature relationship curve, the cumulative wax precipitation amount, and morphology of waxes and asphaltenes. The results indicate that the docosyl polyacrylate@SiO_(2) nanoparticle(PDA@SiO_(2)) can reduce the cumulative wax precipitation amount of crude oil by 72.8%, decline the viscosity of crude oil by 85.6% at 20℃, reduce the average size of wax crystals by 89.7%, and inhibit the agglomeration of asphaltene by 74.8%. Therefore, the nanoparticles not only adjust the crystalline behaviors of waxes, but also inhibit the agglomeration of asphaltenes. Apparently, core-shell hybride nanoparticles provides more heterogeneous nucleation sites for the crystallization of wax molecules,thus inhibiting the formation of three-dimensional network structure. The core-shell polymer@SiO_(2) hybride nanoparticles are one of promising additives for inhibiting crystallization of waxes and agglomeration of asphaltenes in crude oil.展开更多
Entropy Generation Optimization(EGO)attained huge interest of scientists and researchers due to its numerous applications comprised in mechanical engineering,air conditioners,heat engines,thermal machines,heat exchang...Entropy Generation Optimization(EGO)attained huge interest of scientists and researchers due to its numerous applications comprised in mechanical engineering,air conditioners,heat engines,thermal machines,heat exchange,refrigerators,heat pumps and substance mixing etc.Therefore,the study of radiative hybrid nanofluid(GO-MoS_(2)/C_(2)H_(6)O_(2)–H_(2)O)and the conventional nanofluid(MoS_(2)/C_(2)H_(6)O_(2)–H_(2)O)is conducted in the presence of Lorentz forces.The flow configuration is modeled between the parallel rotating plates in which the lower plate is permeable.The models which govern the flow in rotating system are solved numerically over the domain of interest and furnished the results for the temperature,entropy generation and thermophysical characteristics of the hybrid as well as conventional nanofluids,respectively.It is examined that the thermal profile intensifies against stronger thermal radiations and magnetic field.The surface of the plate is heated due to the imposed thermal radiations and magnetic field which cause the increment in the temperature.It is also observed that the temperature declines against more rotating plates.Further,the entropy production increases for more dissipative effects and declines against more magnetized fluid.Thermal conductivities of the hybrid nanofluid enhances promptly in comparison with regular liquid therefore,under consideration hybrid nanofluid is reliable for the heat transfer.Moreover,dominating thermal transport is perceived for the hybrid nanofluid which showed that hybrid suspension GO-MoS_(2)/C_(2)H_(6)O_(2)–H_(2)O is better for industrial,engineering and technological uses.展开更多
The conversion of solar radiation to thermal energy has recently attracted a lot of interest as the requirement for renewable heat and power grows.Due to their enhanced ability to promote heat transmission,nanofluids ...The conversion of solar radiation to thermal energy has recently attracted a lot of interest as the requirement for renewable heat and power grows.Due to their enhanced ability to promote heat transmission,nanofluids can significantly contribute to enhancing the efficiency of solar-thermal systems.This article focus solar energy aspect on the effects of the thermal radiation in the flow of a hyperbolic tangent nanofluid containing magnesium oxide(MgO)and silver(Ag)are the nanoparticle with the base fluid as kerosene through a wedge and stagnation.The system of hybrid nanofluid transport equations are transformed into ordinary differential systems using the appropriate self-similarity transformations.These systems are then determined by using the Runge-Kutta 4th order with shooting technique in the MATLAB solver.Graphs and tables illustrate the effects of significant factors on the fluid transport qualities.The velocity is growths but it is declarations in temperature by increasing values in the power law index parameter.Weissenberg numbers with higher values improve the temperature and velocity in the wedge and stagnation,respectively.The thermal radiation and Eckert number both parameters intensification the rate of heat transfer for wedge and stagnation,respectively.The heat transfer rate in fluid flow over a stagnation point is found to be 14.0346%higher compared to flow over a wedge.Moreover,incorporating hybrid nanoparticles into the base fluid enhances the heat transfer rate by 8.92%for the wedge case and 13.26%for the stagnation point case.展开更多
In this article,the rheology of Ferro-fluid over an axisymmetric heated disc with a variable magnetic field by considering the dispersion of hybrid nanoparticles is considered.The flow is assumed to be produced by the...In this article,the rheology of Ferro-fluid over an axisymmetric heated disc with a variable magnetic field by considering the dispersion of hybrid nanoparticles is considered.The flow is assumed to be produced by the stretching of a rotating heated disc.The contribution of variable thermophysical properties is taken to explore themomentum,mass and thermal transportation.The concept of boundary layermechanismis engaged to reduce the complex problem into a simpler one in the form of coupled partial differential equations system.The complex coupled PDEs are converted into highly nonlinear coupled ordinary differential equations system(ODEs)and the resulting nonlinear flow problem is handled numerically.The solution is obtained via finite element procedure(FEP)and convergence is established by conducting the grid-independent survey.The solution of converted dimensionless problem containing fluid velocity,temperature and concentration field is plotted against numerous involved emerging parameters and their impact is noted.From the obtained solution,it is monitored that higher values of magnetic parameter retard the fluid flow and escalating values of Eckert number results in to enhance temperature profile.Ferro-fluid flow and heat energy for the case of the Yamada Ota hybrid model are higher than for the case of the Hamilton Crosser hybrid model.Developing a model is applicable to the printing process,electronic devices,temperature measurements,engineering process and food-making process.The amount of mass species is reduced vs.incline impacts of chemical reaction and Schmidt parameter.展开更多
Free convection in hybrid nanomaterial-saturated permeable media is crucial in various engineering applications.The present study aims to investigate the free convection of an aqueous-based hybrid nanomaterial through...Free convection in hybrid nanomaterial-saturated permeable media is crucial in various engineering applications.The present study aims to investigate the free convection of an aqueous-based hybrid nanomaterial through a zone under the combined effect of the Lorentz force and radiation.The natural convection of the hybrid nanomaterial is modeled by implementing a control volume finite element method(CVFEM)-based code,whereas Darcy assumptions are used to model the porosity terms in the momentum buoyancy equation involving the average Nusselt number Nu_(ave),flow streamlines,and isotherm profiles.A formula for estimating Nu_(ave) is proposed.The results show that the magnetic force retards the flow,and the fluid tends to attract the magnetic field source.Nu_(ave) is directly correlated with the Rayleigh number and radiation;however,it is indirectly dependent on the Hartmann number.Conduction is the dominant mode at larger Darcy and Hartmann numbers.展开更多
Comprehensive Summary Metal nanoparticles(NPs)decorated block copolymer(BCP)hybrid nanoparticles have attracted enormous attention for their actual value in catalysis,medical therapy,and bioengineering.The confined as...Comprehensive Summary Metal nanoparticles(NPs)decorated block copolymer(BCP)hybrid nanoparticles have attracted enormous attention for their actual value in catalysis,medical therapy,and bioengineering.The confined assembly of BCPs within evaporative emulsion droplet is verified as an effective method to provide polymeric scaffolds to load metal NPs.However,to date,it remains challenging to generate different types of metal NPs decorated BCP hybrid nanoparticles.Herein,we employed the emulsion confined self-assembly of poly(styrene-b-2-vinylpyridine)(PS-b-P2VP)and the followed seed-mediated growth of Au and palladium(Pd)NPs onto well-defined BCP particles to design a series of Au/Pd decorated BCP hybrid nanoparticles,which exhibited excellent catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol with the reductant of NaBH4.This work may inspire more researchers to investigate the selective decoration of different metal NPs onto the polymeric scaffolds,broadening the potential applications of the inorganic/organic hybrid nanoparticles.展开更多
In the present day,there is a growing trend of employing new strategies to synthesize hybrid nanoparticles,which involve combining various functionalities into a single nanocomposite system.These modern methods differ...In the present day,there is a growing trend of employing new strategies to synthesize hybrid nanoparticles,which involve combining various functionalities into a single nanocomposite system.These modern methods differ significantly from the traditional classical approaches and have emerged at the forefront of materials science.The fabrication of hybrid nanomaterials presents an unparalleled opportunity for applica-tions in a wide range of areas,including therapy to diagnosis.The focus of this review article is to shed light on the different modalities of hybrid nanoparticles,providing a concise description of hybrid silver nano-particles,exploring various modes of synthesis and classification of hybrid silver nanoparticles,and highlighting their advantages.Addi-tionally,we discussed core-shell silver nanoparticles and various types of core and shell combinations based on the material category,such as dielectric,metal,or semiconductor.The two primary classes of hybrid silver nanoparticles were also reviewed.Furthermore,various hybrid nanoparticles and their methods of synthesis were discussed but we emphasize silica as a suitable candidate for hybridization alongside metal nanoparticles.This choice is due to its hydrophilic surface qualities and high surface charge,which provide the desired repulsive forces to minimize aggregation between the metal nanoparticles in the liquid solution.Silica shell encapsulation also provides chemical inertness,robustness and the adaptability to the desired hybrid nanoparticle.Therefore,among all the materials used to coat metal nanoparticles;silica is highly approved.展开更多
The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L...The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L1 via inhibiting novo production of PD-L1 will overcome the innate and adaptive PD-L1 expression during chemotherapy,thus enable sustained and efficient immune checkpoint blockade(ICB)to active antitumor immune response.Herein,we designed a glutathione(GSH)-responsive camptothecin(CPT)prodrug-based hybrid micellar nanoparticles(siPD-L1@HM-CPT)to achieve synergistic antitumor chemoimmunotherapy by PD-L1 knockdown.siPD-L1@HM-CPT derived from the one-step loading PD-L1 siRNA(siPD-L1)into the CPT prodrug-based hybrid micelles(HM-CPT)which were co-assembled from biodegradable polyphosphoesters-based prodrug CPT-ss-PAEEP15 and stabilizer DSPE-PEG,showed high loading efficiency,GSH-responsive drug release,and excellent stability and biosafety.siPD-L1@HM-CPT achieved simultaneously the co-delivery of CPT and siPD-L1 in vitro and in vivo,high accumulation at the tumor sites,and rapid intracellular release to promote antitumor efficacy via sensitizing CPT chemotherapy,inducing strong immunogenic cell death(ICD)and sustained ICB to improve intratumoral CD8+T cells infiltration.In addition,the antitumor immunity response limited by the differentiated immunogenicity,intrinsic PD-L1 expression,and intracellular GSH level was facilitated by efficient ICD and ICB from silencing PD-L1 and synergistic CPT chemosensitization in our experimental B16-F10 and 4T1 tumor models.Our study might offer a perspective on designing novel co-delivery nanoparticles by convenient and controllable preparation for antitumor chemo-immunotherapy.展开更多
Assembling and ordering nanomaterials into desirable patterns are considerably significant,since the properties of nanomaterials depend not only on the size and shape,but also on the spatial arrangement among the coll...Assembling and ordering nanomaterials into desirable patterns are considerably significant,since the properties of nanomaterials depend not only on the size and shape,but also on the spatial arrangement among the collective building blocks.In this work,the DNA self-assembly technology of hybridization chain reaction(HCR) provided a convenient method to yield long double-strand DNA(dsDNA) to install gold nanoparticles(AuNPs) into one dimensional assembly along the skeleton of dsDNA.Interestingly,the tunable length of AuNPs assemblies along dsDNA chain could be achieved by adjusting the reaction time of HCR,which is based on the formation of covalent bond between Au and the-SH group of DNA.Compared with weak light scattering of single AuNP,these AuNPs assemblies could be clearly imaged under the dark field microscopy,indicating that the light scattering was greatly improved after assembling.展开更多
This research work explores the effect of hybrid nanoparticles on the flow over a rotating disk by using an activation energy model.Here,we considered molybdenum disulfide and ferro sulfate as nanoparticles suspended ...This research work explores the effect of hybrid nanoparticles on the flow over a rotating disk by using an activation energy model.Here,we considered molybdenum disulfide and ferro sulfate as nanoparticles suspended in base fluid water.The magnetic field is pragmatic normal to the hybrid nanofluid flow direction.The derived nonlinear ordinary differential equations are non-dimensionalized and worked out numerically with the help of Maple software by the RKF-45 method.The scientific results for a non-dimensionalized equation are presented for both nanoparticle and hybrid nanoparticle case.Accoutrements of various predominant restrictions on flow and thermal fields are scanned.Computation estimation for friction factor,local Nusselt number and Sherwood number are also executed.Results reveal that the reduction of the heat transfer rate is greater in hybrid nanoparticles when compared to nanoparticles for increasing values of Eckert Number and the thermal field enhances for the enhanced values of volume fraction.展开更多
Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid na...Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid nanoparticles(LPHNPs) for imaging and treatment in an ortho topic glioma model.LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate(PQC),a mitochondria-targeting small molecule.Compared with the pure nanofiber self-assembled by PQC,LPHNPs not only preserve the comparable antiproliferative potency,but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection.Also,this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes.By integrating the advantages from liposome and PQC molecule,LPHNPs have minimal system toxicity,enhanced potency of photodynamic therapy(PDT) and visualization capacities of drug biodistribution and tumor imaging.The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma.The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.展开更多
Microflowers made of interconnected MnO2 nanosheets have been successfully synthesized in a microwave reactor through a hydrothermal reduction of KMnO4 with aqueous HCI at elevated temperatures in the presence of supe...Microflowers made of interconnected MnO2 nanosheets have been successfully synthesized in a microwave reactor through a hydrothermal reduction of KMnO4 with aqueous HCI at elevated temperatures in the presence of superparamagnetic Fe3O4SiO2 core-shell nanoparticles.Due to the chemical compatibility between SiO2 and MnO2,the heterogeneous reaction leads to the spontaneous encapsulation of the Fe3O4@SiO2 core-shell nanoparticles in the MnO2 microflowers.The resulting hybrid particles exhibit multiple properties including high surface area associated with the MnO2nanosheets and superparamagnetism originated from the Fe3O4@SiO2 core-shell nanoparticles.which are beneficial for applications requiring both high surface area and magnetic separation.展开更多
基金This research is financially supported by the Natural Science Foundation of China(Grant No.81273446).
文摘Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailability.The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles(PLHNs)to enhance the oral absorption of BCS IV drugs.In this paper,taking paclitaxel(PTX)as a drug model,PTX-loaded PLHNs were prepared by a self-assembly method.Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability.Three P-gp inhibitors(D-α-tocopherol polyethylene glycol 1000 succinate,pluronic P123 and Solutol RHS15)were incorporated into selected PLHNs,and a CYP450 inhibitor(the extract of VBRB,BC0)was utilized to jointly promote the drug absorption.Properties of all the PLHNs were characterized systemically,including particle size,zeta potential,encapsulation efficiency,morphology,stability,in vitro drug release,mucoadhesion,in situ intestinal permeability and in vivo systemic exposure.It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested,with absolute bioavailability 21.95%.P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%,8-fold increase compared with that of PTX itself(4.75%).Taken together,our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption,especially for BCS IV drugs.
基金This project was supported by the National Natural Science Foundation of China to K.Y Qiu (Grant No. 29874002) and Outstanding Young Scientist Award to Y. Wei (Grant No. 29825504)
文摘Atom transfer radical polymerization (ATRP) using cuprous chloride/2,2'-bipyridine (bipy) was applied to graft polymerization of styrene on the surface of silica nanoparticles to synthesize polymer-inorganic hybrid nanoparticles, 2-(4Chloromethylphenyl) ethyltriethoxysilane (CTES) was immobilized on the surface of silica nanoparticles through condensation reaction of the silanol groups on silica with triethoxysilane group of CTES. Then ATRP of St was initiated by this surface-modified silica nanoparticles bearing benzyl chloride groups, and formed PSt graft chains on the surface of silica nanoparticles. The thickness of the graft chains increased with reaction time. End group analysis confirmed the occurrence of ATRP. Thermal analysis indicated that thermal stabilization of these resulting hybrid nanoparticles also increases with polymerization conversion. The results above show that this 'grafting from' reaction could be used for the preparation of polymer-inorganic hybrid nanoparticles with controlled structure of the polymer's end groups.
文摘Particulate carriers such as polymeric micelles (PMs) and liposomes have been investigated to increase drug accumulation in tumors and reduce distribution to healthy tissues. In this study, we prepared PM and hybrid nanoparticles (HNPs) with poly(ethylene oxide)-block-poly(methacrylic acid) (PEO-b-PMAA) for loading cisplatin, and evaluated cisplatin release, cytotoxicity, and biodistribution in mice. PM composed of PEO-b-PMAA and HNPs composed of egg phosphatidylcholine (EPC)/PEO-b-PMAA at molar ratios of 50/2.8 (HNP-P5) and 50/50 (HNP-P50), respectively, were prepared by a nanoprecipitation method. The sizes of PM, HNP-P5, and HNP-P50 after inclusion of cisplatin were approximately 200, 100, and 55 nm, respectively, and their entrapment efficiencies were approximately 44% - 66%. In the drug-release study, HNP-P5 and HNP-P50 showed reduced release of cisplatin compared with PM. Regarding the cytotoxic assay, HNP-P5 exhibited lower cytotoxicity for mouse Lewis lung carcinoma (LLC) and mouse colon carcinoma Colon 26 cells than PM and HNP-P50. In terms of biodistribution, PM could significantly improve blood circulation and tumor accumulation after intravenous injection into Colon 26 tumor-bearing mice compared with free cisplatin, but HNP-P5 and HNP-P50 did not. EPC in HNPs might be destabilized in the circulation, although it could reduce release of cisplatin in in vitro experiments. This study suggested that polymeric micelles composed of PEO-b-PMAA are a better carrier for cisplatin than hybrid nanoparticles composed of PEO-b-PMAA and EPC.
基金This work was financially supported by the National Natural Science Foundation of China(No.81803466)the Natural Science Foundation of Guangdong Province(No.2018A030310095,China)the Key Areas Research and Development Program of Guangdong Province(No.2019B020204002,China).
文摘The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.
基金funded by grants from the Global Core Research Center(GCRC,Grant No.2011-0030001)of the National Research Foundation(NRF),Ministry of Science and ICT(MSIT),Republic of Koreathe MSIT,Republic of Korea(NRF-2018R1A2A1A05019203+1 种基金NRF-2018R1A5A2024425)the Korean Health Technology R&D Project(No.HI19C0664),Ministry of Health&Welfare,Republic of Korea
文摘Conjugation of antibodies to nanoparticles allows specific cancer targeting,but conventional conjugation methods generate heterogeneous conjugations that cannot guarantee the optimal orientation and functionality of the conjugated antibody.Here,a molecular engineering technique was used for sitespecific conjugation of antibodies to nanoparticles.We designed an anti-claudin 3(CLDN3)antibody containing a single cysteine residue,h4 G3 cys,then linked it to the maleimide group of lipid polydopamine hybrid nanoparticles(LPNs).Because of their negatively charged lipid coating,LPNs showed high colloidal stability and provided a functional surface for site-specific conjugation of h4 G3 cys.The activity of h4 G3 cys was tested by measuring the binding of h4 G3 cys-conjugated LPNs(C-LPNs)to CLDN3-positive tumor cells and assessing its subsequent photothermal effects.C-LPNsspecifically recognized CLDN3-overexpressing T47 D breast cancer cells but not CLDN3-negative Hs578 T breast cancer cells.High binding of C-LPNs to CLDN3-overexpressing T47 D cells resulted in significantly higher temperature generation upon NIR irradiation and potent anticancer photothermal efficacy.Consistent with this,intravenous injection of C-LPNsin a T47 D xenograft mouse model followed by NIR irradiation caused remarkable tumor ablation compared with other treatments through high temperature increases.Our results establish an accurate antibody-linking method and demonstrate the possibility of developing therapeutics using antibody-guided nanoparticles.
文摘Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceuticalpreparations such as controlled release formulations, parenteral preparations, surgicaltreatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticlesfor topical and site targeting delivery of Norfloxacin by emulsification solvent evaporationmethod (ESE). The design of experiment (DOE) was done by using software to optimize the result, andthen a surface plot was generated to compare with the practical results. The surface morphology, particlesize, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized bySEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterizedby DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited anaverage particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution withpolydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymerhybrid nanoparticles were confirmed by zeta potential, showed the value from t23.4 ± 1.5 mVto t41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonasaeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these two.Lipid-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in24 h. A stability study of the optimized formulation showed the suitable condition for the storage oflipid-polymer hybrid nanoparticles was at 4 ± 2 C/60 ± 5% RH. These results illustrated high potential oflipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.
基金supported by the National Natural Science Foundation of China(No. 21574037)the"100 Talents" Program of Hebei Province, China(No. E2014100004)+2 种基金the Natural Science Foundation of Hebei Province(Nos. B2015202330, B2017202051)the Program for Top 100 Innovative Talents in Colleges and Universities of Hebei Province(No.SLRC2017028)the Tianjin Natural Science Foundation(No. 15JCYBJC17500)
文摘A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)-co-(2-(D-galactose)methylmethacryl-ate)](P(MACPTS-co-MAGP)) and AgNPs is developed to deliver the anti-cancer drug camptothecin(CPT) and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer sidechains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence( "off" state) due to the nanoparticle surface energy transfer(NSET) effect.Upon the exposure to glutathione(GSH), the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT("on" state). The system offers a platform to track the CPT delivery and releasing in real time
基金the financial support received form National Natural Science Foundation of China(No.82073784)Jilin Province Science and Technology Development Program(No.20200801012GH)Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province(No.2019C050-4).
文摘Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This study developed bifunctional oral lipid polymer hybrid nanoparticles(R8-PEG-PPNPs)that deliver superoxide dismutase(SOD)for the treatment of ulcerative colitis(UC).R8-PEG-PPNPs was composed of PCADK,PLGA,lecithin,and co-modified with stearic acid-octa-arginine and polyethylene glycol.The nanoparticles(NPs)are uniformly dispersed with a complete spherical structure.In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection.In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000µg/mL and promote cellular uptake.In experiments with ulcerative colitis mice,R8-PEG-PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation.Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs.
基金Financial support by project of China Petroleum Engineering Corp., Ltd (CPEC), Study on microstructural regulation of polyacrylate and applying as pour-point depressant for crude oil (2021ZYGC-01-01)。
文摘The gelation of crude oil with high wax and asphaltene content at low temperatures often results in the block of transportation pipeline in Africa. In recent years, it was reported that surface hydrophobicmodified nanoparticles have important applications in crude oil flow modification. In this work, four kinds of core-shell hybride nanoparticles by grafting poly(octadecyl, docosyl acrylate) and poly(acrylate-α-olefin) onto the surface of nano-sized SiO_(2) were synthesized by grafting polymerization method.The chemical structure of nanoparticles was analyzed by Fourier transform infrared spectroscopy(FT-IR),scanning electron microscopy(SEM) and thermogravimetric analysis(TGA). The rheological behaviors of crude oil and precipitation of asphaltenes in the presence of nanoparticles were studied by measuring the viscose-temperature relationship curve, the cumulative wax precipitation amount, and morphology of waxes and asphaltenes. The results indicate that the docosyl polyacrylate@SiO_(2) nanoparticle(PDA@SiO_(2)) can reduce the cumulative wax precipitation amount of crude oil by 72.8%, decline the viscosity of crude oil by 85.6% at 20℃, reduce the average size of wax crystals by 89.7%, and inhibit the agglomeration of asphaltene by 74.8%. Therefore, the nanoparticles not only adjust the crystalline behaviors of waxes, but also inhibit the agglomeration of asphaltenes. Apparently, core-shell hybride nanoparticles provides more heterogeneous nucleation sites for the crystallization of wax molecules,thus inhibiting the formation of three-dimensional network structure. The core-shell polymer@SiO_(2) hybride nanoparticles are one of promising additives for inhibiting crystallization of waxes and agglomeration of asphaltenes in crude oil.
文摘Entropy Generation Optimization(EGO)attained huge interest of scientists and researchers due to its numerous applications comprised in mechanical engineering,air conditioners,heat engines,thermal machines,heat exchange,refrigerators,heat pumps and substance mixing etc.Therefore,the study of radiative hybrid nanofluid(GO-MoS_(2)/C_(2)H_(6)O_(2)–H_(2)O)and the conventional nanofluid(MoS_(2)/C_(2)H_(6)O_(2)–H_(2)O)is conducted in the presence of Lorentz forces.The flow configuration is modeled between the parallel rotating plates in which the lower plate is permeable.The models which govern the flow in rotating system are solved numerically over the domain of interest and furnished the results for the temperature,entropy generation and thermophysical characteristics of the hybrid as well as conventional nanofluids,respectively.It is examined that the thermal profile intensifies against stronger thermal radiations and magnetic field.The surface of the plate is heated due to the imposed thermal radiations and magnetic field which cause the increment in the temperature.It is also observed that the temperature declines against more rotating plates.Further,the entropy production increases for more dissipative effects and declines against more magnetized fluid.Thermal conductivities of the hybrid nanofluid enhances promptly in comparison with regular liquid therefore,under consideration hybrid nanofluid is reliable for the heat transfer.Moreover,dominating thermal transport is perceived for the hybrid nanofluid which showed that hybrid suspension GO-MoS_(2)/C_(2)H_(6)O_(2)–H_(2)O is better for industrial,engineering and technological uses.
文摘The conversion of solar radiation to thermal energy has recently attracted a lot of interest as the requirement for renewable heat and power grows.Due to their enhanced ability to promote heat transmission,nanofluids can significantly contribute to enhancing the efficiency of solar-thermal systems.This article focus solar energy aspect on the effects of the thermal radiation in the flow of a hyperbolic tangent nanofluid containing magnesium oxide(MgO)and silver(Ag)are the nanoparticle with the base fluid as kerosene through a wedge and stagnation.The system of hybrid nanofluid transport equations are transformed into ordinary differential systems using the appropriate self-similarity transformations.These systems are then determined by using the Runge-Kutta 4th order with shooting technique in the MATLAB solver.Graphs and tables illustrate the effects of significant factors on the fluid transport qualities.The velocity is growths but it is declarations in temperature by increasing values in the power law index parameter.Weissenberg numbers with higher values improve the temperature and velocity in the wedge and stagnation,respectively.The thermal radiation and Eckert number both parameters intensification the rate of heat transfer for wedge and stagnation,respectively.The heat transfer rate in fluid flow over a stagnation point is found to be 14.0346%higher compared to flow over a wedge.Moreover,incorporating hybrid nanoparticles into the base fluid enhances the heat transfer rate by 8.92%for the wedge case and 13.26%for the stagnation point case.
文摘In this article,the rheology of Ferro-fluid over an axisymmetric heated disc with a variable magnetic field by considering the dispersion of hybrid nanoparticles is considered.The flow is assumed to be produced by the stretching of a rotating heated disc.The contribution of variable thermophysical properties is taken to explore themomentum,mass and thermal transportation.The concept of boundary layermechanismis engaged to reduce the complex problem into a simpler one in the form of coupled partial differential equations system.The complex coupled PDEs are converted into highly nonlinear coupled ordinary differential equations system(ODEs)and the resulting nonlinear flow problem is handled numerically.The solution is obtained via finite element procedure(FEP)and convergence is established by conducting the grid-independent survey.The solution of converted dimensionless problem containing fluid velocity,temperature and concentration field is plotted against numerous involved emerging parameters and their impact is noted.From the obtained solution,it is monitored that higher values of magnetic parameter retard the fluid flow and escalating values of Eckert number results in to enhance temperature profile.Ferro-fluid flow and heat energy for the case of the Yamada Ota hybrid model are higher than for the case of the Hamilton Crosser hybrid model.Developing a model is applicable to the printing process,electronic devices,temperature measurements,engineering process and food-making process.The amount of mass species is reduced vs.incline impacts of chemical reaction and Schmidt parameter.
文摘Free convection in hybrid nanomaterial-saturated permeable media is crucial in various engineering applications.The present study aims to investigate the free convection of an aqueous-based hybrid nanomaterial through a zone under the combined effect of the Lorentz force and radiation.The natural convection of the hybrid nanomaterial is modeled by implementing a control volume finite element method(CVFEM)-based code,whereas Darcy assumptions are used to model the porosity terms in the momentum buoyancy equation involving the average Nusselt number Nu_(ave),flow streamlines,and isotherm profiles.A formula for estimating Nu_(ave) is proposed.The results show that the magnetic force retards the flow,and the fluid tends to attract the magnetic field source.Nu_(ave) is directly correlated with the Rayleigh number and radiation;however,it is indirectly dependent on the Hartmann number.Conduction is the dominant mode at larger Darcy and Hartmann numbers.
基金the financial support of the Natural Science Foundation of China(52003070)Zhejiang Provincial Natural Science Foundation of China(LR20E030003).
文摘Comprehensive Summary Metal nanoparticles(NPs)decorated block copolymer(BCP)hybrid nanoparticles have attracted enormous attention for their actual value in catalysis,medical therapy,and bioengineering.The confined assembly of BCPs within evaporative emulsion droplet is verified as an effective method to provide polymeric scaffolds to load metal NPs.However,to date,it remains challenging to generate different types of metal NPs decorated BCP hybrid nanoparticles.Herein,we employed the emulsion confined self-assembly of poly(styrene-b-2-vinylpyridine)(PS-b-P2VP)and the followed seed-mediated growth of Au and palladium(Pd)NPs onto well-defined BCP particles to design a series of Au/Pd decorated BCP hybrid nanoparticles,which exhibited excellent catalytic activity for the reduction of 4-nitrophenol to 4-aminophenol with the reductant of NaBH4.This work may inspire more researchers to investigate the selective decoration of different metal NPs onto the polymeric scaffolds,broadening the potential applications of the inorganic/organic hybrid nanoparticles.
文摘In the present day,there is a growing trend of employing new strategies to synthesize hybrid nanoparticles,which involve combining various functionalities into a single nanocomposite system.These modern methods differ significantly from the traditional classical approaches and have emerged at the forefront of materials science.The fabrication of hybrid nanomaterials presents an unparalleled opportunity for applica-tions in a wide range of areas,including therapy to diagnosis.The focus of this review article is to shed light on the different modalities of hybrid nanoparticles,providing a concise description of hybrid silver nano-particles,exploring various modes of synthesis and classification of hybrid silver nanoparticles,and highlighting their advantages.Addi-tionally,we discussed core-shell silver nanoparticles and various types of core and shell combinations based on the material category,such as dielectric,metal,or semiconductor.The two primary classes of hybrid silver nanoparticles were also reviewed.Furthermore,various hybrid nanoparticles and their methods of synthesis were discussed but we emphasize silica as a suitable candidate for hybridization alongside metal nanoparticles.This choice is due to its hydrophilic surface qualities and high surface charge,which provide the desired repulsive forces to minimize aggregation between the metal nanoparticles in the liquid solution.Silica shell encapsulation also provides chemical inertness,robustness and the adaptability to the desired hybrid nanoparticle.Therefore,among all the materials used to coat metal nanoparticles;silica is highly approved.
基金The authors acknowledge the support by the National Basic Research Program of China(Nos.2020YFA0710700 and 2018YFA0208900)the National Natural Science Foundation of China(No.31470968).
文摘The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L1 via inhibiting novo production of PD-L1 will overcome the innate and adaptive PD-L1 expression during chemotherapy,thus enable sustained and efficient immune checkpoint blockade(ICB)to active antitumor immune response.Herein,we designed a glutathione(GSH)-responsive camptothecin(CPT)prodrug-based hybrid micellar nanoparticles(siPD-L1@HM-CPT)to achieve synergistic antitumor chemoimmunotherapy by PD-L1 knockdown.siPD-L1@HM-CPT derived from the one-step loading PD-L1 siRNA(siPD-L1)into the CPT prodrug-based hybrid micelles(HM-CPT)which were co-assembled from biodegradable polyphosphoesters-based prodrug CPT-ss-PAEEP15 and stabilizer DSPE-PEG,showed high loading efficiency,GSH-responsive drug release,and excellent stability and biosafety.siPD-L1@HM-CPT achieved simultaneously the co-delivery of CPT and siPD-L1 in vitro and in vivo,high accumulation at the tumor sites,and rapid intracellular release to promote antitumor efficacy via sensitizing CPT chemotherapy,inducing strong immunogenic cell death(ICD)and sustained ICB to improve intratumoral CD8+T cells infiltration.In addition,the antitumor immunity response limited by the differentiated immunogenicity,intrinsic PD-L1 expression,and intracellular GSH level was facilitated by efficient ICD and ICB from silencing PD-L1 and synergistic CPT chemosensitization in our experimental B16-F10 and 4T1 tumor models.Our study might offer a perspective on designing novel co-delivery nanoparticles by convenient and controllable preparation for antitumor chemo-immunotherapy.
基金supported by the National Natural Science Foundation of China(21535006,21405123)
文摘Assembling and ordering nanomaterials into desirable patterns are considerably significant,since the properties of nanomaterials depend not only on the size and shape,but also on the spatial arrangement among the collective building blocks.In this work,the DNA self-assembly technology of hybridization chain reaction(HCR) provided a convenient method to yield long double-strand DNA(dsDNA) to install gold nanoparticles(AuNPs) into one dimensional assembly along the skeleton of dsDNA.Interestingly,the tunable length of AuNPs assemblies along dsDNA chain could be achieved by adjusting the reaction time of HCR,which is based on the formation of covalent bond between Au and the-SH group of DNA.Compared with weak light scattering of single AuNP,these AuNPs assemblies could be clearly imaged under the dark field microscopy,indicating that the light scattering was greatly improved after assembling.
基金financial support from Dr D S Kothari Post-Doctoral Fellowship Scheme,University Grants Commission,New Delhi。
文摘This research work explores the effect of hybrid nanoparticles on the flow over a rotating disk by using an activation energy model.Here,we considered molybdenum disulfide and ferro sulfate as nanoparticles suspended in base fluid water.The magnetic field is pragmatic normal to the hybrid nanofluid flow direction.The derived nonlinear ordinary differential equations are non-dimensionalized and worked out numerically with the help of Maple software by the RKF-45 method.The scientific results for a non-dimensionalized equation are presented for both nanoparticle and hybrid nanoparticle case.Accoutrements of various predominant restrictions on flow and thermal fields are scanned.Computation estimation for friction factor,local Nusselt number and Sherwood number are also executed.Results reveal that the reduction of the heat transfer rate is greater in hybrid nanoparticles when compared to nanoparticles for increasing values of Eckert Number and the thermal field enhances for the enhanced values of volume fraction.
基金support from NIH/NCI(R01CA199668,R01CA232845)NIH/NIDCR(1R01DE029237,USA)+1 种基金NIH/NICHD(R01HD086195,USA)UC Davis Comprehensive Cancer Centre Support Grant(CCSG,USA)awarded by the National Cancer Institute(NCI P30CA093373,USA)。
文摘Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles.Here we developed a kind of lipid-small molecule hybrid nanoparticles(LPHNPs) for imaging and treatment in an ortho topic glioma model.LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate(PQC),a mitochondria-targeting small molecule.Compared with the pure nanofiber self-assembled by PQC,LPHNPs not only preserve the comparable antiproliferative potency,but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection.Also,this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes.By integrating the advantages from liposome and PQC molecule,LPHNPs have minimal system toxicity,enhanced potency of photodynamic therapy(PDT) and visualization capacities of drug biodistribution and tumor imaging.The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma.The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.
基金supported by the U.S.Department of Energy,Office of Science,Office of Basic Energy Sciences,under Contract No.DE-AC02-06CH11357
文摘Microflowers made of interconnected MnO2 nanosheets have been successfully synthesized in a microwave reactor through a hydrothermal reduction of KMnO4 with aqueous HCI at elevated temperatures in the presence of superparamagnetic Fe3O4SiO2 core-shell nanoparticles.Due to the chemical compatibility between SiO2 and MnO2,the heterogeneous reaction leads to the spontaneous encapsulation of the Fe3O4@SiO2 core-shell nanoparticles in the MnO2 microflowers.The resulting hybrid particles exhibit multiple properties including high surface area associated with the MnO2nanosheets and superparamagnetism originated from the Fe3O4@SiO2 core-shell nanoparticles.which are beneficial for applications requiring both high surface area and magnetic separation.