The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used ...The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.展开更多
Stable and monodispersed silver nanoparticles were produced through a mild,convenient,one-pot method based on the reduction of silver nitrate in the presence of poly(amic acid) (PAA) as a stabilizer.The surface plasma...Stable and monodispersed silver nanoparticles were produced through a mild,convenient,one-pot method based on the reduction of silver nitrate in the presence of poly(amic acid) (PAA) as a stabilizer.The surface plasma band transition was monitored along with time in the reaction mixture for three sets of experiments by ultraviolet-visible spectroscopy.Analysis of the data with the Avrami equation yielded n exponent with values between 0.5 and 1.5,demonstrating three-dimensional heterogeneous nucleation and diffusion-controlled growth,accompanied by soft impingement effect.XRD and TEM analyses show a softly agglomerated polycrystalline state and a nearly spherical morphology (<50 nm) of nanoparticles.The FT-IR result indicates that the PAA molecular structure could be hardly influenced by the formation of nanoparticles.展开更多
Objective: To prepare and characterize poly lactic-co-glycolic acid(PLGA) nanoparticles loaded with soluble leishmanial antigen or autoclaved leishmanial antigen and explore in vitro and in vivo immunogenicity of anti...Objective: To prepare and characterize poly lactic-co-glycolic acid(PLGA) nanoparticles loaded with soluble leishmanial antigen or autoclaved leishmanial antigen and explore in vitro and in vivo immunogenicity of antigen encapsulated nanoparticles. Methods: Water/oil/water double emulsion technique was employed to synthesize PLGA nanoparticles, and scanning electron microscopy, Fourier transform infrared spectroscopy and Zeta-potential measurements were used to identify the characteristics of nanoparticles. Cytotoxicity of synthetized nanoparticles on J774 macrophage were investigated by MTT assays. To determine the in vitro immunostimulatory efficacies of nanoparticles, griess reaction and ELISA was used to measure the amounts of NO and cytokines. During the in vivo analysis, Balb/c mice were immunized with vaccine formulations, and protective properties of nanoparticles were measured by Leishman Donovan unit in the liver following the infection. Cytokine levels in spleens of mice were determined by ELISA. Results: MTT assay showed that neither soluble leishmanial antigen nor autoclaved leishmanial antigen encapsulated nanoparticles showed cytotoxicity against J774 macrophage cells. Contrary to free antigens, both autoclaved leishmanial antigen-nanoparticle and soluble leishmanial antigen-nanoparticle formulations led to a 10 and 16-fold increase in NO amounts by macrophages, respectively. Leishman Donovan unit calculations revealed that soluble leishmanial antigen-nanoparticles and autoclaved leishmanial antigen-nanoparticles yielded 52% and 64% protection against visceral leishmaniasis in mouse models. Besides, in vitro and in vivo tests demonstrated that by increasing IFN-γ and IL-12 levels and inhibiting IL-4 and IL-10 secretions, autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigennanoparticles triggered Th1 immune response. Conclusions: Both autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigen-nanoparticles formulations provide exceptional in vitro and in vivo immunostimulatory activities. Hence, PLGA-based antigen delivery systems are recommended as potential vaccine candidates against visceral leishmaniasis.展开更多
Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficac...Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.展开更多
The objective of this study was to investigate the influences of organic solvents on particle size, drug content, loading efficiency and yield for 5 Fluorouracil Poly(lactic acid) nanoparticles . The 5 Fluorouracil wa...The objective of this study was to investigate the influences of organic solvents on particle size, drug content, loading efficiency and yield for 5 Fluorouracil Poly(lactic acid) nanoparticles . The 5 Fluorouracil was entrapped into poly(lactic acid)(PLA) nanoparticles using a water in oil in water solvent evaporation technique. During the preparation process, ethyl acetate and acetone were used as organic solvents since they are less toxic than the more commonly used dichloromethane. The effect of the three solvents on particle size, drug content, loading efficiency and yield of nanopartcles was compared. When the solvent of the oil phase was acetone, the highest drug content, smallest particle size and lowest yield were obtained for the PLA nanoparticles.展开更多
Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits...Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.展开更多
An important area of research in nanotechnology deals with the synthesis of nanoparticles of different chemical compositions,sizes and controlled monodispersity.Currently,there is a growing need to develop environment...An important area of research in nanotechnology deals with the synthesis of nanoparticles of different chemical compositions,sizes and controlled monodispersity.Currently,there is a growing need to develop environmentally benign nanoparticle synthesis in which no toxic chemicals are used in the synthesis protocol.Palladium nanoparticles(Pd Np) are of interest because of their catalytic properties and affinity for hydrogen.Our protocol for the phyto-synthesis of Pd Np under moderate p H and room temperature offers a new means to develop environmentally benign nanoparticles.Solanum trilobatum is enlightened in our present study as it is enriched with phytochemicals to reduce palladium chloride ions.Poly MVA a dietary supplement based on the nontoxic chemotherapeutic lipoic acid-palladium complex(LA-Pd) is been hypothesized as the new paradigm of cancer therapy.Hence forth we successfully conjugated lipoic acid(S-Pd Np-LA) and vitamins(S-Pd Np-Vitamin-LA) to palladium nanoparticles synthesised from Solanum trilobatum leaf extract.These nanoparticles(S-Pd Np,S-Pd Np-LA,S-Pd Np-Vitamin-LA) were characterized with UV-Vis Spectroscopy,SEM and FTIR analysis,which revealed that S-Pd Np are polydisperse and of different morphologies ranging from 60?70 nm(S-Pd Np),65?80 nm(S-Pd Np-LA) and 75?100 nm(S-Pd Np-Vitamin-LA) in size.展开更多
The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid)(PLGA) nanoparticles(TPNs) was studied. Stabilizer-free nanoprecipitation met...The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid)(PLGA) nanoparticles(TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt(PSS) as anionic layer and poly(allylamine hydrochloride)(PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs(4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of –57.8 m V. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs(4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.展开更多
AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1...AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1α si RNA) between MSCs and retinal pigment epithelial cells(RPE) under hypoxia environment.METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α si RNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles(PLGA-NPs) through the water-in-oil-in-water(w/o/w) multiple emulsion technique. The effect of PLGANPs uptake on the expression of HIF-1α m RNA was tested in RPE cells by real-time quantitative polymerase chain reaction(q PCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α si RNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using q PCR at the time points 24h, 3d, and 7d.RESULTS: The average diameter of PLGA-NPs loaded with HIF si RNA was 314.1 nm and the zeta potential was-0.36 m V. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α si RNA can effectively reduce the expression of HIF-1α m RNA up to 7d in RPE(0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation(2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%;F=0.70, P=0.53) and migration(124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSCloaded HIF-1α si RNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α m RNA expression in RPE cells could continue until the 7th day, the level of HIF-1α m RNA was lower than that of other groups(F=171.98, P<0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α si RNA carried by MSCs is found to be beneficial temporally for HIF-1α m RNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α si RNA nanoparticles is a potential method for therapy against choroidal neovascularization.展开更多
OBJECTIVE To formulate atractylodin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles and characterize the prepared nanoparticle formulation.METHODS The nanoparticle formulation was developed using solvent displ...OBJECTIVE To formulate atractylodin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles and characterize the prepared nanoparticle formulation.METHODS The nanoparticle formulation was developed using solvent displacement method.The encapsulation and loading efficiency were characterized and particle size,and zeta potential were determined by dynamic light scattering technique.Drug release was assessed in vitro.RESULTS The size(mean±SD of diameter) of the prepared atractylodin-loaded PLGA nanoparticles were(161.27 ± 1.87)nm with narrow size distribution(mean PDI:0.068±0.015) and zeta potential(28.83±0.35)mV.The encapsulation and loading efficiency were(48.31±0.83)% and(2.15±0.04)%,respectively.Drug release from atractylodin-loaded PLGA nanoparticles was observed up to(87.70±0.47)% in 72 h with biphasic manner.Moreover,the nanoparticles were found to be freely dispersible in water without aggregation.CONCLUSION Results suggest that PLGA nanoparticles may be used as an effective drug delivery system for atractylodin.The anti-cholangiocarcinoma activity of this nanoparticle formulation is required.展开更多
Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody dru...Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.展开更多
The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunologi...The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.展开更多
Biocompatible magnetic nanoparticles were prepared by co-precipitation method in the presence of poly(aspartic acid)(PAsp)as stabilizer,which was one of the most extensively studied and used poly(amino acids).As a bio...Biocompatible magnetic nanoparticles were prepared by co-precipitation method in the presence of poly(aspartic acid)(PAsp)as stabilizer,which was one of the most extensively studied and used poly(amino acids).As a biocompatible dispersant,PAsp was successfully attached to the Fe_(3)O_(4) nanoparticles,which was approved by Fourier transform infrared spectroscopy(FTIR),transmission electron microscopy(TEM)and thermogravimetric analysis(TGA).From X-ray diffraction(XRD)and vibrating sample magnetometry(VSM)measurement results,it was found that PAsp stabilized iron oxide nanoparticles possess excellent Fe_(3)O_(4) crystal structure and superparamagnetic property.Compared with trisodium citrate stabilized magnetic nanoparticles,PAsp stabilized magnetic nanoparticles were biocompatible and with lower cytotoxicity,which makes it more applicable in medicine,biology and biomaterial science.展开更多
A novel electrogenerated chemiluminescence (ECL) aptasensor for highly sensitive detection of thrombin was developed on the basis of poly(pyrrole-co-pyrrole propylic acid) nanoparticles loaded with aptamer and rutheni...A novel electrogenerated chemiluminescence (ECL) aptasensor for highly sensitive detection of thrombin was developed on the basis of poly(pyrrole-co-pyrrole propylic acid) nanoparticles loaded with aptamer and ruthenium complex. Thrombin binding aptamers served as the molecular recognition elements and ruthenium bis(2,2′-bipyridine) (2,2′-bipyridine-4,4′-dicarboxylic acid)-ethylenediamine (Ru1) was used as an ECL signal complex. Novel electroactive polymers poly(pyrrole-co-pyrrole propylic acid) nanoparticles (Ppy-pa NPs) were synthesized by a simple alcohol-assisted microemulsion polymerization. Ru1-Ppy-pa NPs were synthesized by covalently coupling Ru1 with the Ppy-pa NPs. Ppy-pa NPs and Ru1-Ppy-pa NPs were characterized using a fourier transform infrared spectrometer, super-conducting fourier digital NMR spectrometer, and transmission electron microscope. One ECL chemical sensor fabricated by immobilizing the Ru1-Ppy-pa NPs on PIGE was developed for the determination of TprA with a high sensitivity and stability. The ECL aptasensor was fabricated by covalently coupling the thrombin binding aptamer-I (TBA-I) onto the surface of the paraffin-impregnated graphite electrode, which had been covalently modified with a monolayer of 4-aminobenzene sulfonic acid via electrochemical oxidations, for capturing thrombin onto the electrode and then the TBA-II labeled with Ru1-Ppy-pa NPs was bound with epitope of thrombin. The ECL aptasensor showed an extremely low detection limit of 3.0×l0?16 mol/L for thrombin and a good selectivity. This work demonstrated that using Ppy-pa NPs as a carrier of ruthenium complex and molecular recognition element was a promising approach for the fabrication of ECL biosensor with high sensitivity.展开更多
In this research, a surface imprinting strategy has been adopted in protein imprinting. Bovine hemo-globin surface-imprinted polystyrene (PS) nanoparticles with magnetic susceptibility have been syn-thesized through m...In this research, a surface imprinting strategy has been adopted in protein imprinting. Bovine hemo-globin surface-imprinted polystyrene (PS) nanoparticles with magnetic susceptibility have been syn-thesized through multistage core-shell polymerization system using 3-aminophenylboronic acid (APBA) as functional and cross-linking monomers. Superparamagnetic molecularly imprinted polystyrene nanospheres with poly(APBA) thin films have been synthesized and used for the first time for protein molecular imprinting in an aqueous solution. The magnetic susceptibility is imparted through the successful encapsulation of Fe3O4 nanoparticles. The morphology, adsorption, and recognition prop-erties of superparamagnetic molecularly imprinted polymers (MIPs) have been investigated using transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, and vibrating sample magnetometer. Rebinding experimental results show that poly(APBA) MIPs-coated superparamagnetic PS nanoparticles have high adsorption capacity for template protein bovine hemoglobin and compara-tively low nonspecific adsorption. The imprinted superparamagnetic nanoparticles could easily reach the adsorption equilibrium and achieve magnetic separation in an external magnetic field, thus avoid-ing some problems of the bulk polymer.展开更多
The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building...The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.展开更多
文摘The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.
基金Project(10JJ5057)supported by the Hunan Provincial Natural Science Foundation of China
文摘Stable and monodispersed silver nanoparticles were produced through a mild,convenient,one-pot method based on the reduction of silver nitrate in the presence of poly(amic acid) (PAA) as a stabilizer.The surface plasma band transition was monitored along with time in the reaction mixture for three sets of experiments by ultraviolet-visible spectroscopy.Analysis of the data with the Avrami equation yielded n exponent with values between 0.5 and 1.5,demonstrating three-dimensional heterogeneous nucleation and diffusion-controlled growth,accompanied by soft impingement effect.XRD and TEM analyses show a softly agglomerated polycrystalline state and a nearly spherical morphology (<50 nm) of nanoparticles.The FT-IR result indicates that the PAA molecular structure could be hardly influenced by the formation of nanoparticles.
基金supported by Scientific and Technological Research Council of Turkey(TUBITAK,Grant No.213S148)
文摘Objective: To prepare and characterize poly lactic-co-glycolic acid(PLGA) nanoparticles loaded with soluble leishmanial antigen or autoclaved leishmanial antigen and explore in vitro and in vivo immunogenicity of antigen encapsulated nanoparticles. Methods: Water/oil/water double emulsion technique was employed to synthesize PLGA nanoparticles, and scanning electron microscopy, Fourier transform infrared spectroscopy and Zeta-potential measurements were used to identify the characteristics of nanoparticles. Cytotoxicity of synthetized nanoparticles on J774 macrophage were investigated by MTT assays. To determine the in vitro immunostimulatory efficacies of nanoparticles, griess reaction and ELISA was used to measure the amounts of NO and cytokines. During the in vivo analysis, Balb/c mice were immunized with vaccine formulations, and protective properties of nanoparticles were measured by Leishman Donovan unit in the liver following the infection. Cytokine levels in spleens of mice were determined by ELISA. Results: MTT assay showed that neither soluble leishmanial antigen nor autoclaved leishmanial antigen encapsulated nanoparticles showed cytotoxicity against J774 macrophage cells. Contrary to free antigens, both autoclaved leishmanial antigen-nanoparticle and soluble leishmanial antigen-nanoparticle formulations led to a 10 and 16-fold increase in NO amounts by macrophages, respectively. Leishman Donovan unit calculations revealed that soluble leishmanial antigen-nanoparticles and autoclaved leishmanial antigen-nanoparticles yielded 52% and 64% protection against visceral leishmaniasis in mouse models. Besides, in vitro and in vivo tests demonstrated that by increasing IFN-γ and IL-12 levels and inhibiting IL-4 and IL-10 secretions, autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigennanoparticles triggered Th1 immune response. Conclusions: Both autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigen-nanoparticles formulations provide exceptional in vitro and in vivo immunostimulatory activities. Hence, PLGA-based antigen delivery systems are recommended as potential vaccine candidates against visceral leishmaniasis.
基金supported by National Natural Science Foundation of China (No. 51373168)
文摘Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.
文摘The objective of this study was to investigate the influences of organic solvents on particle size, drug content, loading efficiency and yield for 5 Fluorouracil Poly(lactic acid) nanoparticles . The 5 Fluorouracil was entrapped into poly(lactic acid)(PLA) nanoparticles using a water in oil in water solvent evaporation technique. During the preparation process, ethyl acetate and acetone were used as organic solvents since they are less toxic than the more commonly used dichloromethane. The effect of the three solvents on particle size, drug content, loading efficiency and yield of nanopartcles was compared. When the solvent of the oil phase was acetone, the highest drug content, smallest particle size and lowest yield were obtained for the PLA nanoparticles.
文摘Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.
文摘An important area of research in nanotechnology deals with the synthesis of nanoparticles of different chemical compositions,sizes and controlled monodispersity.Currently,there is a growing need to develop environmentally benign nanoparticle synthesis in which no toxic chemicals are used in the synthesis protocol.Palladium nanoparticles(Pd Np) are of interest because of their catalytic properties and affinity for hydrogen.Our protocol for the phyto-synthesis of Pd Np under moderate p H and room temperature offers a new means to develop environmentally benign nanoparticles.Solanum trilobatum is enlightened in our present study as it is enriched with phytochemicals to reduce palladium chloride ions.Poly MVA a dietary supplement based on the nontoxic chemotherapeutic lipoic acid-palladium complex(LA-Pd) is been hypothesized as the new paradigm of cancer therapy.Hence forth we successfully conjugated lipoic acid(S-Pd Np-LA) and vitamins(S-Pd Np-Vitamin-LA) to palladium nanoparticles synthesised from Solanum trilobatum leaf extract.These nanoparticles(S-Pd Np,S-Pd Np-LA,S-Pd Np-Vitamin-LA) were characterized with UV-Vis Spectroscopy,SEM and FTIR analysis,which revealed that S-Pd Np are polydisperse and of different morphologies ranging from 60?70 nm(S-Pd Np),65?80 nm(S-Pd Np-LA) and 75?100 nm(S-Pd Np-Vitamin-LA) in size.
基金supported by grants from the National Natural Science Foundation of China(No.81101690)Natural Science Foundation of Hubei Province(No.2014CFB403)Applied Basic Research Foundation of Wuhan Science and Technology Committee(No.2014060101010034)
文摘The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid)(PLGA) nanoparticles(TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt(PSS) as anionic layer and poly(allylamine hydrochloride)(PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs(4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of –57.8 m V. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs(4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.
基金Supported by Key Research and Development Program of Shaanxi ProvinceChina (No.2020SF-267)+3 种基金the Natural Science Basis Research Plan in Shaanxi Province of China (No.2022JM-514)Bethune·Lumitin Research Funding for the Young and Middle-aged Ophthalmologists (No.BJ-LM2021011J)Xi’an Science and Technology Project [No.20YXYJ0008(3)]Research Incubation Fund of Xi’an People’s Hospital (Xi’an Fourth Hospital)(No.ZD-5, ZD-7, and ZD-8)。
文摘AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1α si RNA) between MSCs and retinal pigment epithelial cells(RPE) under hypoxia environment.METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α si RNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles(PLGA-NPs) through the water-in-oil-in-water(w/o/w) multiple emulsion technique. The effect of PLGANPs uptake on the expression of HIF-1α m RNA was tested in RPE cells by real-time quantitative polymerase chain reaction(q PCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α si RNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using q PCR at the time points 24h, 3d, and 7d.RESULTS: The average diameter of PLGA-NPs loaded with HIF si RNA was 314.1 nm and the zeta potential was-0.36 m V. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α si RNA can effectively reduce the expression of HIF-1α m RNA up to 7d in RPE(0.63±0.05 at 7d, P<0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation(2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%;F=0.70, P=0.53) and migration(124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSCloaded HIF-1α si RNA PLGA-NPs and other groups. The inhibition of PLGA on the HIF-1α m RNA expression in RPE cells could continue until the 7th day, the level of HIF-1α m RNA was lower than that of other groups(F=171.98, P<0.001). CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α si RNA carried by MSCs is found to be beneficial temporally for HIF-1α m RNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α si RNA nanoparticles is a potential method for therapy against choroidal neovascularization.
基金supported by Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma,Chulabhorn International College of Medicine,Thammasat University the National Research University Project of Thailand(NRU)
文摘OBJECTIVE To formulate atractylodin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles and characterize the prepared nanoparticle formulation.METHODS The nanoparticle formulation was developed using solvent displacement method.The encapsulation and loading efficiency were characterized and particle size,and zeta potential were determined by dynamic light scattering technique.Drug release was assessed in vitro.RESULTS The size(mean±SD of diameter) of the prepared atractylodin-loaded PLGA nanoparticles were(161.27 ± 1.87)nm with narrow size distribution(mean PDI:0.068±0.015) and zeta potential(28.83±0.35)mV.The encapsulation and loading efficiency were(48.31±0.83)% and(2.15±0.04)%,respectively.Drug release from atractylodin-loaded PLGA nanoparticles was observed up to(87.70±0.47)% in 72 h with biphasic manner.Moreover,the nanoparticles were found to be freely dispersible in water without aggregation.CONCLUSION Results suggest that PLGA nanoparticles may be used as an effective drug delivery system for atractylodin.The anti-cholangiocarcinoma activity of this nanoparticle formulation is required.
基金funded by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.820LH027)the Hainan Provincial Natural Science Foundation of China(No.823RC472)+1 种基金the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2021WNLOKF008)the Hainan University Scientific Research Foundation(KYQD(ZR)19107).
文摘Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.
基金financially supported by the CAMS Initiative for Innovative Medicine(Grant Number 2017-I2M3-022)Central basic scientific research in colleges and universities(Grant Number 3332019162)+1 种基金the National Natural Science Foundation of China(Grant Number 81503117)the Foundation for Studying Abroad from the China Scholarship Council(Grant Number 201808110121)
文摘The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.20974023,21034003 and 51073040)Shanghai Committee of Science and Technology,China(Grant No.10XD1400500).
文摘Biocompatible magnetic nanoparticles were prepared by co-precipitation method in the presence of poly(aspartic acid)(PAsp)as stabilizer,which was one of the most extensively studied and used poly(amino acids).As a biocompatible dispersant,PAsp was successfully attached to the Fe_(3)O_(4) nanoparticles,which was approved by Fourier transform infrared spectroscopy(FTIR),transmission electron microscopy(TEM)and thermogravimetric analysis(TGA).From X-ray diffraction(XRD)and vibrating sample magnetometry(VSM)measurement results,it was found that PAsp stabilized iron oxide nanoparticles possess excellent Fe_(3)O_(4) crystal structure and superparamagnetic property.Compared with trisodium citrate stabilized magnetic nanoparticles,PAsp stabilized magnetic nanoparticles were biocompatible and with lower cytotoxicity,which makes it more applicable in medicine,biology and biomaterial science.
基金supported by the National Natural Science Foundation of China (21027007, 20975065 & 20775046)
文摘A novel electrogenerated chemiluminescence (ECL) aptasensor for highly sensitive detection of thrombin was developed on the basis of poly(pyrrole-co-pyrrole propylic acid) nanoparticles loaded with aptamer and ruthenium complex. Thrombin binding aptamers served as the molecular recognition elements and ruthenium bis(2,2′-bipyridine) (2,2′-bipyridine-4,4′-dicarboxylic acid)-ethylenediamine (Ru1) was used as an ECL signal complex. Novel electroactive polymers poly(pyrrole-co-pyrrole propylic acid) nanoparticles (Ppy-pa NPs) were synthesized by a simple alcohol-assisted microemulsion polymerization. Ru1-Ppy-pa NPs were synthesized by covalently coupling Ru1 with the Ppy-pa NPs. Ppy-pa NPs and Ru1-Ppy-pa NPs were characterized using a fourier transform infrared spectrometer, super-conducting fourier digital NMR spectrometer, and transmission electron microscope. One ECL chemical sensor fabricated by immobilizing the Ru1-Ppy-pa NPs on PIGE was developed for the determination of TprA with a high sensitivity and stability. The ECL aptasensor was fabricated by covalently coupling the thrombin binding aptamer-I (TBA-I) onto the surface of the paraffin-impregnated graphite electrode, which had been covalently modified with a monolayer of 4-aminobenzene sulfonic acid via electrochemical oxidations, for capturing thrombin onto the electrode and then the TBA-II labeled with Ru1-Ppy-pa NPs was bound with epitope of thrombin. The ECL aptasensor showed an extremely low detection limit of 3.0×l0?16 mol/L for thrombin and a good selectivity. This work demonstrated that using Ppy-pa NPs as a carrier of ruthenium complex and molecular recognition element was a promising approach for the fabrication of ECL biosensor with high sensitivity.
基金Supported by the National High-Tech Research & Development Program of China (Grant No. 2007AA10Z432)the National Basic Research Program (Grant No. 2007CB914100)+1 种基金the National Natural Science Foundation of China (Grant Nos. 20675040 & 20875050)the Natural Science Foundation of Tianjin (Grant No. 07JCYBJC00500)
文摘In this research, a surface imprinting strategy has been adopted in protein imprinting. Bovine hemo-globin surface-imprinted polystyrene (PS) nanoparticles with magnetic susceptibility have been syn-thesized through multistage core-shell polymerization system using 3-aminophenylboronic acid (APBA) as functional and cross-linking monomers. Superparamagnetic molecularly imprinted polystyrene nanospheres with poly(APBA) thin films have been synthesized and used for the first time for protein molecular imprinting in an aqueous solution. The magnetic susceptibility is imparted through the successful encapsulation of Fe3O4 nanoparticles. The morphology, adsorption, and recognition prop-erties of superparamagnetic molecularly imprinted polymers (MIPs) have been investigated using transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, and vibrating sample magnetometer. Rebinding experimental results show that poly(APBA) MIPs-coated superparamagnetic PS nanoparticles have high adsorption capacity for template protein bovine hemoglobin and compara-tively low nonspecific adsorption. The imprinted superparamagnetic nanoparticles could easily reach the adsorption equilibrium and achieve magnetic separation in an external magnetic field, thus avoid-ing some problems of the bulk polymer.
基金supported by grants from the Ministry of Science and ICT, Republic of Korea (NRF-2018R1A2A1A05019203 and NRF-2018R1A5A2024425)from the Korean Health Technology R&D Project (Nos. HI15C2842 and HI18C2177)Ministry of Health & Welfare, Republic of Korea
文摘The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.