Eco-friendly and biodegradable novel hydrogel were prepared by blending and solution casting method. The designed hydrogel is based on chitosan/ PEG600/Gurgam with carbon nanofiller along silane crosslinked (TEOS) wit...Eco-friendly and biodegradable novel hydrogel were prepared by blending and solution casting method. The designed hydrogel is based on chitosan/ PEG600/Gurgam with carbon nanofiller along silane crosslinked (TEOS) with pH sensitive response to controlled release of drug in biomedical materials and agriculture industry. The various concentration of carbon nanofiller is used to analyze its effect on the fabricated hydrogel characteristics by using FTIR, SEM, TGA, swelling studies (water, buffer and ionic solution). Spectra of FTIR reflected both established and newly developed groups (like hydrogel). COOH group presence is clearly observed in this range in the carbon filler reinforced hydrogel. The SEM micrographs show that CPG0.003 had a collection of polysaccharide chains as thin helices, which is attributed to the increase in the size of porosity. TGA shows to increase concentration of nanofiller enhanced the thermal stability of the designed hydrogels at temperature 25˚C to 550˚C mass loss percentage decrease upto 20% and increase thermal stability. This pH response made these resultant hydrogels as fruitful competitor against the many reported controlled release application.展开更多
A new kind of biodegradable pH-sensitive drug delivery system was developed via chitosan-albumin conjugate hydrogel. Through changing the feeding modes of reactants, two types of hydrogels(comb-type and reticular-typ...A new kind of biodegradable pH-sensitive drug delivery system was developed via chitosan-albumin conjugate hydrogel. Through changing the feeding modes of reactants, two types of hydrogels(comb-type and reticular-type) were synthesized by amidation reactions between 6-O-succinoylated N-phthaloyl chitosan and albumin. The structures and morphologies of the hydrogels were characterized by SEM. And their water swelling capacity, drug loading and releasing properties at different pH values were also investigated. It was found that the comb-type of hydrogels with looser space construction had better water swelling ratio(more than 400% of its original mass) than the reticular-type of ones did(about 180% of its original mass). In vitro release experiments of Rifampicin show that the hydrogels provided the controlled release of the entrapped drug for more than 50 h. The drug release rates of both types of hydrogels under acidic condition were lower than those under neutral or basic condition. The introduction of albumin not only improved the hydrophilicity of chitosan, but also provided the possibility of the carrier system combining other biologically active materials more easily to fulfill the delivery and therapy functions.展开更多
Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the ...Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol( PVA)hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.展开更多
Currently,the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy,owing to its precise structure,high drug loading and improved oral bioavailability via overcoming various physiologic ...Currently,the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy,owing to its precise structure,high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract,blood circulation and tumor tissues compared to other oral nanomedicines.Herein,this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes,which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters.The precise nano-prodrugs exhibit extraordinarily high drug loading(68.16%),electric neutrality,strong hydrophobicity,and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH.These favorable physicochemical properties can effectively facilitate gastrointestinal absorption,blood circulation stability,tumor accumulation,cellular uptake,and cytotoxicity,therefore achieving high oral relative bioavailability(358.72%)and significant tumor growth inhibition while decreasing side effects.Thus,this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.展开更多
We use the carbon nanotube (CNT) as the material of the pH sensing layer of the separative structure for the extended gate H^+-ion sensitive field effect transistor (EGFET) device.The CNT paste was prepared with CNT p...We use the carbon nanotube (CNT) as the material of the pH sensing layer of the separative structure for the extended gate H^+-ion sensitive field effect transistor (EGFET) device.The CNT paste was prepared with CNT powder,Ag powder,silicagel,the di-n-butyl phthalate and the toluene solvents by appropriate ratio,then immobilized on the silicon substrate to form the carbon nanotube sensing layer.We measured theⅠ_(DS)-Ⅴ_G curves of the carbon nanotube separative structure EGFET device in the different pH buffer solutions by the Keithley 236Ⅰ-Ⅴmeasurement system.According to the experimental results,we can obtain the pH sensitivities of the carbon nanotube separative structure EGFET device,which is 62.54mV/pH from pH1 to pH13.展开更多
The pH /temperature dually responsive microgels of interpenetrating polymer network( IPN) structure composed of poly( N-isopropylacrylamide)( PNIPAM) network and poly( acrylic acid)( PAA) network( PNIPAM /PAA IPN micr...The pH /temperature dually responsive microgels of interpenetrating polymer network( IPN) structure composed of poly( N-isopropylacrylamide)( PNIPAM) network and poly( acrylic acid)( PAA) network( PNIPAM /PAA IPN microgels) were synthesized by seed emulsion polymerization. The results obtained by dynamic laser light scattering( DLLS) show that the microgels have good pH /temperature dual sensitivities. The temperature sensitive component and the pH sensitive component inside the microgels have little interference with each other. The rheological properties of the concentrated PNIPAM /PAA IPN microgel dispersions as a function of temperature at pH 4. 0 or 7. 0 were investigated by viscometer,and the results displayed that only at pH 7. 0 the dispersions presented thermoreversible thickening behavior. Then the PNIPAM /PAA fibers were prepared by self-assembly of the PNIPAM /PAA IPN microgels in the ice-crystal templates formed by unidirectional liquid nitrogen freezing method. Field emission scanning electron microscopy( FESEM) images indicate that the PNIPAM /PAA fibers are rounded,randomly orientated and interweaved.展开更多
A novel type of polysoap hydrogel based on poly(tetraethylenepentamine-epichlorohydrin)hydrophobically modified by stearic acid was prepared. The deswelling behaviors of polysoap hydrogels werestudied by immersing the...A novel type of polysoap hydrogel based on poly(tetraethylenepentamine-epichlorohydrin)hydrophobically modified by stearic acid was prepared. The deswelling behaviors of polysoap hydrogels werestudied by immersing the gels in buffer solution at various pHs and ionic species. The deswelling of the gelsdid not depend on the cationic species of electrolyte but depended strongly on the anionic species. Acomparison of polysoap gels with the gel unmodified hydrophobically verified the importance of hydrophobicinteraction, which enhances the occurrence of deswelling rate.展开更多
Electrical conductivity and pH sensitivity of nano-PANI membrane was studied. In this work,an ordered porous nano-polyaniline/acrylate gel polymer( PAGP) membrane was prepared from methyl methacrylate( MMA)/acrylic ac...Electrical conductivity and pH sensitivity of nano-PANI membrane was studied. In this work,an ordered porous nano-polyaniline/acrylate gel polymer( PAGP) membrane was prepared from methyl methacrylate( MMA)/acrylic acid( AA)/nano-PANI bicontinuous microemulsions. The morphology,electric conductivity and p H sensitivity of the composite membrane were studied using scanning electronic microscopy,atomic force microscopy,and electrochemical impedance spectroscopy. It was found that the polymer matrix comprises of two types of proton migrating tunnels: interconnect hydrophilic trench( IHT) and continuous amphiphilic matrix( CAM). The increase of doped nano-PANI particles in those channels leads to a formation of three dimension grain-boundary network. It contributes to the short response time and good reversibility of the sensors. Impedance changes in the low-frequency region reveal an inductive behavior to PANI membrane,which maybe the contribution of faradaic pseudocapacitance of the polymer materials.展开更多
A low molecular weight gelator with dual pH and glucose sensitive moieties was synthesized. The gelator penetrated in the mesopores of silica nanoparticles(MSNs) and formed low molecular weight gel(LMWG) as gate to fa...A low molecular weight gelator with dual pH and glucose sensitive moieties was synthesized. The gelator penetrated in the mesopores of silica nanoparticles(MSNs) and formed low molecular weight gel(LMWG) as gate to fabricate dual pH and glucose responsive nano drug delivery system. Antidiabetic drug was loaded in the gel caped MSNs, the drug release was responsive to the pH and glucose levels and the drug release could be controlled via the stimuli sensitivity of gel.展开更多
An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification (RCA) was developed for prostate cancer membrane antigen (PSMA) targeted cancer therapy. The template ...An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification (RCA) was developed for prostate cancer membrane antigen (PSMA) targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain (multiple GC-pair sequences) of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experi- ments, treated with doxorubicin loaded DNA nanoparti- cles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.展开更多
pH-sensitive wettability of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) self assembled films, exhibiting superoleophobicity under water and hydrophilicity at low pH value, and oleophobicity under water and hyd...pH-sensitive wettability of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) self assembled films, exhibiting superoleophobicity under water and hydrophilicity at low pH value, and oleophobicity under water and hydrophobicity at neutral condition, has been realized. The wettability properties resulted from the surface topological and chemical transition, which were confirmed by in situ AFM measurements under water at different pH. At low pH, P4VP chains, which were confined in the hexagonal-packed nanodomains, got protonated into a swollen state, while at high pH, P4VP chains were deprotonated into a collapsed state. The reversible protonation/deprotonation procedure on the molecular scale leads to surface topological and chemical transition, thereby pH-sensitive wettability.展开更多
A series of cross-linked gels of Poly(N-isopropylacrylamide) [P(NIPAAm)] and Poly(methacr-ylic acid)[P(MAA)] homopolymers and P(NIPAAm-co-MAA) random copolymers were synthesized based on NIPAAm and MAA using...A series of cross-linked gels of Poly(N-isopropylacrylamide) [P(NIPAAm)] and Poly(methacr-ylic acid)[P(MAA)] homopolymers and P(NIPAAm-co-MAA) random copolymers were synthesized based on NIPAAm and MAA using 4,4-Bis-(methacryloylamino) azobenzene (BMAAB) as a cross-linker. The swelling behavior of these hydrogels in different pH buffer solutions was studied. The influential factors of the gels including composition of NIPAAm and MAA, pH and temperature upon swelling behavior were investigated. The obtained gels not only hold pH and thermometrical sensitivity, but also take on enzymatic sensitivity due to the cross-linker could be degraded by enzymes of colon. Swelling equilibrium degree of copolymers was very low in acidic medium, which could avoid drug releasing due to biggish swelling of carder in stomach. Hydrogels would partly swell owing to higher pH value in small intestine. When arrived in colon, hydrogels completely swelled, meanwhile, azoenzymes located would degrade azo-bonds of polymeric network and then drug released in colon.展开更多
Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for...Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin(DOX) using a p H-responsive ionic-complementary octapeptide FOE.This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at p H 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence.展开更多
As nano-scale drug delivery systems,smart micelles that are sensitive to specific biological environment and allowed for target site-triggered drug release by reversible stabilization of micelle structure are attracti...As nano-scale drug delivery systems,smart micelles that are sensitive to specific biological environment and allowed for target site-triggered drug release by reversible stabilization of micelle structure are attractive.In this work,a biocompatible and pH-sensitive copolymer is synthesized through bridging poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)block and poly(D,L-lactide)(PLA)block by a benzoyl imine linkage(Blink).Biomimetic micelles with excellent biocompatibility based on such PLA-Blink-PMPC copolymer are prepared as carriers for paclitaxel(PTX)delivery.Due to the rapid breakage of the benzoyl imine linkage under acidic condition,the micelle structure is disrupted with accelerated PTX release.Such pH-sensitive triggered drug release behavior in synchronization with acidic conditions at tumor site is helpful for improving the utilization of drug and facilitating antitumor efficacy.These micelles can be used as promising drug delivery systems due to their biocompatible and smart properties.展开更多
A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N'-methylene-bis-(acrylamide) as a cross-linker. Their swelling b...A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N'-methylene-bis-(acrylamide) as a cross-linker. Their swelling behavior in different pH buffer solutions and colonic enzymatic degradability were studied. The obtained results show that these hydrogels have good pH sensitivity which can avoid drug release in stomach, and their swelling kinetics in stimulant intestinal environment follow second-order swelling kinetics equation. The factors influencing the swelling kinetics include the degree of cross-linking and the composition, which may control no release or a little amount release of drug inside the hydrogels in the small intestine by tailoring these factors. The gels are degradable by colonic enzymes and there is a correlativity between the degradation of networks and the swelling degree of the gels, which may trigger the release of drug in the colon. The hydrogels show a great potential for their application in oral colon-specific drug delivery system.展开更多
The thermosensitive poly ( N-isopropylacrylamide ) (PNIPAAm) and poly (N-isopropylacrylamide-co-acrylamide) [ poly (NIPAAm-co-AAm) ] hydrogels with different acrylamide molar percentage are prepared by radiati...The thermosensitive poly ( N-isopropylacrylamide ) (PNIPAAm) and poly (N-isopropylacrylamide-co-acrylamide) [ poly (NIPAAm-co-AAm) ] hydrogels with different acrylamide molar percentage are prepared by radiation polymerization using Co^60 γ-ray. Their swelling equilibrium data in the media of deionized water, NaCl aqueous solutions and different pH buffer solutions are determined. It appears that lower critical solution temperature (LCST) of the hydrogels will drop with the increase of ionic strength and increase with the rising of acrylamide content, A semi-empirical formula is set up with the experimental results. Moreover, it also indicates that this copolymer is pH-sensitive, which is similar to the homopolymer of PNIPAAm.展开更多
OBJECTIVE To explore a novel pH-sensitive fluorescent probe for in vivo tumor imaging.METHODS Zn5 were obtained in 140℃ after mixed with Me OH,water,Zn(NO_3)2·6 H_2O,H4L and trimethylamine.The fluorescence spect...OBJECTIVE To explore a novel pH-sensitive fluorescent probe for in vivo tumor imaging.METHODS Zn5 were obtained in 140℃ after mixed with Me OH,water,Zn(NO_3)2·6 H_2O,H4L and trimethylamine.The fluorescence spectra of Zn5 with the same concentration in different pH aqueous solutions were detected.And the stability of Zn5 was investigated by time dependent fluorescence emission spectra of Zn5 in BSA aqueous solution and 5.0% serum solution.Then,the cytotoxicity of Zn5 was detected by MTT assays.To clarify whether a similar fluorescence response occurs in biological organisms,He La cells were pretreated with probe Zn5(0.5 μmol·L^(-1)) and fluorescence imaging were collected for targeting lysosomes in living cells because of lysosomes′ acidic microenvironment.The A375 tumor-bearing mice were used to assess the imaging ability of Zn5 in vivo.Mouse tumor xenografts were established by injection of A375 cells with 2×10~6 cells per flank.Probe(1 μg·g^(-1)) was administered to mice by injection.Images were obtained using IVIS Spectrum CT Imaging System.RESULTS There is a 11-fold intensity increasing as the pH values changing from 8 to 2.The almost unchanged emission intensities suggest Zn5 is stable in both BSA and serum.Zn5 has negligible cytotoxicity for He La,293 T and CHO-K1 cells.Zn5 can selectively display lysosomes in living cells.Both the 2D and 3D images in vivo distinguish the tumor from other tissues with good fluorescence contrast.CONCLUSION The high chemical stability,emission in the Vis/NIR range,pH sensitivity,a pKa located in the tumor pH range,and low toxicity make Zn5 is suitable for application as a pH-sensitive fluorescent probe for bio-imaging.展开更多
Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and dru...Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped CQDs.Lipo/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.展开更多
A novel fluorinated triblock copolymer incorporating 2-ethylhexyl methacrylate (EHMA), tert-butyl methacrylate (tBMA) and 1H,1H,2H,2H-perfluorodecyl acrylate (FA) (PEHMA-b-PtBMA-b-PFA) was first synthesized us...A novel fluorinated triblock copolymer incorporating 2-ethylhexyl methacrylate (EHMA), tert-butyl methacrylate (tBMA) and 1H,1H,2H,2H-perfluorodecyl acrylate (FA) (PEHMA-b-PtBMA-b-PFA) was first synthesized using three successive reversible addition fragmentation chain transfer (RAFT) polymerization and the subsequent hydrolyzing at acidic condition. The as-fabricated triblock copolymer exhibited an interesting morphology evolution from the multi-compartment rod-like structure to spherical structure along with the addition of a selective solution. At the same time, a visible phase separation domain could be seen in the core area due to the existence of fluorocarbon segments. Furthermore, the self- assembly behavior of the triphilic copolymer at different pH was also verified by transmission electron microscopy, as well as the dynamic light scattering. These stimuli-responsive multi-compartment nanostructures may have potential applications in drug delivery.展开更多
Robust cytosolic protein delivery requires both efficient protein binding with delivery vehicles and effective protein release after cell internalization.Although a variety of stimuli-responsive carriers have been des...Robust cytosolic protein delivery requires both efficient protein binding with delivery vehicles and effective protein release after cell internalization.Although a variety of stimuli-responsive carriers have been designed,simultaneously integrating these two functions in one versatile carrier is challenging.Herein,we developed a polyamidoamine(PAMAM)-based polymer with an intracellular pHactuated hydrophobic-to-hydrophilic transition for this purpose.展开更多
文摘Eco-friendly and biodegradable novel hydrogel were prepared by blending and solution casting method. The designed hydrogel is based on chitosan/ PEG600/Gurgam with carbon nanofiller along silane crosslinked (TEOS) with pH sensitive response to controlled release of drug in biomedical materials and agriculture industry. The various concentration of carbon nanofiller is used to analyze its effect on the fabricated hydrogel characteristics by using FTIR, SEM, TGA, swelling studies (water, buffer and ionic solution). Spectra of FTIR reflected both established and newly developed groups (like hydrogel). COOH group presence is clearly observed in this range in the carbon filler reinforced hydrogel. The SEM micrographs show that CPG0.003 had a collection of polysaccharide chains as thin helices, which is attributed to the increase in the size of porosity. TGA shows to increase concentration of nanofiller enhanced the thermal stability of the designed hydrogels at temperature 25˚C to 550˚C mass loss percentage decrease upto 20% and increase thermal stability. This pH response made these resultant hydrogels as fruitful competitor against the many reported controlled release application.
基金Supported by the National Basic Research Program of China(No.2009CB930102)the National High-Tech Research and Development Program of China(No.2007AA03Z535)+4 种基金the National Natural Science Foundation of China(Nos.20774094 20874097)the "100 Talents Program" of the Chinese Academy of Sciences(No.KGCX2-YW-802)the Project of Jilin Provincial Science and Technology Department China(No.20082104).
文摘A new kind of biodegradable pH-sensitive drug delivery system was developed via chitosan-albumin conjugate hydrogel. Through changing the feeding modes of reactants, two types of hydrogels(comb-type and reticular-type) were synthesized by amidation reactions between 6-O-succinoylated N-phthaloyl chitosan and albumin. The structures and morphologies of the hydrogels were characterized by SEM. And their water swelling capacity, drug loading and releasing properties at different pH values were also investigated. It was found that the comb-type of hydrogels with looser space construction had better water swelling ratio(more than 400% of its original mass) than the reticular-type of ones did(about 180% of its original mass). In vitro release experiments of Rifampicin show that the hydrogels provided the controlled release of the entrapped drug for more than 50 h. The drug release rates of both types of hydrogels under acidic condition were lower than those under neutral or basic condition. The introduction of albumin not only improved the hydrophilicity of chitosan, but also provided the possibility of the carrier system combining other biologically active materials more easily to fulfill the delivery and therapy functions.
基金National Natural Science Foundation of China(No.31271028)Shanghai Nano Science Program,China(No.11nm0505500)+1 种基金Innovation Program of Shanghai M unicipal Education Commission,China(No.13ZZ051)Chinese Universities Scientific Fund,China(No.EG2014023)
文摘Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol( PVA)hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.
基金supported by the Anhui Engineering Technology Research Center of Biochemical Pharmaceutical(Bengbu Medical College)the National Natural Science Foundation of China(No.51803001)+1 种基金the Research Foundation of Education Department of Anhui Province of China(No.KJ2018ZD003,KJ2018A0006 and KJ2019A0015)the Academic and Technology Introduction Project of Anhui University(AU02303203).
文摘Currently,the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy,owing to its precise structure,high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract,blood circulation and tumor tissues compared to other oral nanomedicines.Herein,this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes,which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters.The precise nano-prodrugs exhibit extraordinarily high drug loading(68.16%),electric neutrality,strong hydrophobicity,and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH.These favorable physicochemical properties can effectively facilitate gastrointestinal absorption,blood circulation stability,tumor accumulation,cellular uptake,and cytotoxicity,therefore achieving high oral relative bioavailability(358.72%)and significant tumor growth inhibition while decreasing side effects.Thus,this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.
文摘We use the carbon nanotube (CNT) as the material of the pH sensing layer of the separative structure for the extended gate H^+-ion sensitive field effect transistor (EGFET) device.The CNT paste was prepared with CNT powder,Ag powder,silicagel,the di-n-butyl phthalate and the toluene solvents by appropriate ratio,then immobilized on the silicon substrate to form the carbon nanotube sensing layer.We measured theⅠ_(DS)-Ⅴ_G curves of the carbon nanotube separative structure EGFET device in the different pH buffer solutions by the Keithley 236Ⅰ-Ⅴmeasurement system.According to the experimental results,we can obtain the pH sensitivities of the carbon nanotube separative structure EGFET device,which is 62.54mV/pH from pH1 to pH13.
基金National Natural Science Foundations of China(Nos.51073033,51373030)the Fundamental Research Funds for the Central Universities,China(No.2232014D3-43)
文摘The pH /temperature dually responsive microgels of interpenetrating polymer network( IPN) structure composed of poly( N-isopropylacrylamide)( PNIPAM) network and poly( acrylic acid)( PAA) network( PNIPAM /PAA IPN microgels) were synthesized by seed emulsion polymerization. The results obtained by dynamic laser light scattering( DLLS) show that the microgels have good pH /temperature dual sensitivities. The temperature sensitive component and the pH sensitive component inside the microgels have little interference with each other. The rheological properties of the concentrated PNIPAM /PAA IPN microgel dispersions as a function of temperature at pH 4. 0 or 7. 0 were investigated by viscometer,and the results displayed that only at pH 7. 0 the dispersions presented thermoreversible thickening behavior. Then the PNIPAM /PAA fibers were prepared by self-assembly of the PNIPAM /PAA IPN microgels in the ice-crystal templates formed by unidirectional liquid nitrogen freezing method. Field emission scanning electron microscopy( FESEM) images indicate that the PNIPAM /PAA fibers are rounded,randomly orientated and interweaved.
基金This work is financially supported by National Natural Science Foundation of China.
文摘A novel type of polysoap hydrogel based on poly(tetraethylenepentamine-epichlorohydrin)hydrophobically modified by stearic acid was prepared. The deswelling behaviors of polysoap hydrogels werestudied by immersing the gels in buffer solution at various pHs and ionic species. The deswelling of the gelsdid not depend on the cationic species of electrolyte but depended strongly on the anionic species. Acomparison of polysoap gels with the gel unmodified hydrophobically verified the importance of hydrophobicinteraction, which enhances the occurrence of deswelling rate.
基金Sponsored by the National Natural Science Foundation of China(Grant No.51571093)the Fundamental Research Funds for the Central Universities(Grant No.2015ZM094)
文摘Electrical conductivity and pH sensitivity of nano-PANI membrane was studied. In this work,an ordered porous nano-polyaniline/acrylate gel polymer( PAGP) membrane was prepared from methyl methacrylate( MMA)/acrylic acid( AA)/nano-PANI bicontinuous microemulsions. The morphology,electric conductivity and p H sensitivity of the composite membrane were studied using scanning electronic microscopy,atomic force microscopy,and electrochemical impedance spectroscopy. It was found that the polymer matrix comprises of two types of proton migrating tunnels: interconnect hydrophilic trench( IHT) and continuous amphiphilic matrix( CAM). The increase of doped nano-PANI particles in those channels leads to a formation of three dimension grain-boundary network. It contributes to the short response time and good reversibility of the sensors. Impedance changes in the low-frequency region reveal an inductive behavior to PANI membrane,which maybe the contribution of faradaic pseudocapacitance of the polymer materials.
基金the National Natural Science Foundation of China(No.21672164)the Natural Science Foundation of Zhejiang Province(No.LY15B020001)for the financial support
文摘A low molecular weight gelator with dual pH and glucose sensitive moieties was synthesized. The gelator penetrated in the mesopores of silica nanoparticles(MSNs) and formed low molecular weight gel(LMWG) as gate to fabricate dual pH and glucose responsive nano drug delivery system. Antidiabetic drug was loaded in the gel caped MSNs, the drug release was responsive to the pH and glucose levels and the drug release could be controlled via the stimuli sensitivity of gel.
文摘An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification (RCA) was developed for prostate cancer membrane antigen (PSMA) targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain (multiple GC-pair sequences) of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experi- ments, treated with doxorubicin loaded DNA nanoparti- cles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.
基金financially supported by the National Natural Science Foundation of China(No.21204002)Specialized Research Fund for the Doctoral Program of Higher Education(No.20111102120050)+1 种基金Program for New Century Excellent Talents in Universities(2010)the Fundamental Research Funds for the Central Universities
文摘pH-sensitive wettability of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) self assembled films, exhibiting superoleophobicity under water and hydrophilicity at low pH value, and oleophobicity under water and hydrophobicity at neutral condition, has been realized. The wettability properties resulted from the surface topological and chemical transition, which were confirmed by in situ AFM measurements under water at different pH. At low pH, P4VP chains, which were confined in the hexagonal-packed nanodomains, got protonated into a swollen state, while at high pH, P4VP chains were deprotonated into a collapsed state. The reversible protonation/deprotonation procedure on the molecular scale leads to surface topological and chemical transition, thereby pH-sensitive wettability.
文摘A series of cross-linked gels of Poly(N-isopropylacrylamide) [P(NIPAAm)] and Poly(methacr-ylic acid)[P(MAA)] homopolymers and P(NIPAAm-co-MAA) random copolymers were synthesized based on NIPAAm and MAA using 4,4-Bis-(methacryloylamino) azobenzene (BMAAB) as a cross-linker. The swelling behavior of these hydrogels in different pH buffer solutions was studied. The influential factors of the gels including composition of NIPAAm and MAA, pH and temperature upon swelling behavior were investigated. The obtained gels not only hold pH and thermometrical sensitivity, but also take on enzymatic sensitivity due to the cross-linker could be degraded by enzymes of colon. Swelling equilibrium degree of copolymers was very low in acidic medium, which could avoid drug releasing due to biggish swelling of carder in stomach. Hydrogels would partly swell owing to higher pH value in small intestine. When arrived in colon, hydrogels completely swelled, meanwhile, azoenzymes located would degrade azo-bonds of polymeric network and then drug released in colon.
基金supported by the National Natural Science Foundation of China (Nos. 81572978 and 81760638)Special Science and Frontier Technology Research Project of Chongqing(No. cstc2016jcyj A0520)+1 种基金Innovative Technology in Military and Clinical Medicine (No. 2018JSLC0035)Natural Science Foundation of Xinjiang Province (No. 2017D01C200)。
文摘Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin(DOX) using a p H-responsive ionic-complementary octapeptide FOE.This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at p H 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence.
基金This research was financially supported by National Natural Science Foundation of China(Projects 51403131,21502129)Sichuan Province Science and Technology Support Program(2016SZ0004)+1 种基金China Postdoctoral Science Foundation Funded Project(2015M570783)the National 111 Project of Introducing Talents of Discipline to Universities(No.B16033).
文摘As nano-scale drug delivery systems,smart micelles that are sensitive to specific biological environment and allowed for target site-triggered drug release by reversible stabilization of micelle structure are attractive.In this work,a biocompatible and pH-sensitive copolymer is synthesized through bridging poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)block and poly(D,L-lactide)(PLA)block by a benzoyl imine linkage(Blink).Biomimetic micelles with excellent biocompatibility based on such PLA-Blink-PMPC copolymer are prepared as carriers for paclitaxel(PTX)delivery.Due to the rapid breakage of the benzoyl imine linkage under acidic condition,the micelle structure is disrupted with accelerated PTX release.Such pH-sensitive triggered drug release behavior in synchronization with acidic conditions at tumor site is helpful for improving the utilization of drug and facilitating antitumor efficacy.These micelles can be used as promising drug delivery systems due to their biocompatible and smart properties.
基金Funded by the National Natural Science Foundation of China (No.50503019)
文摘A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N'-methylene-bis-(acrylamide) as a cross-linker. Their swelling behavior in different pH buffer solutions and colonic enzymatic degradability were studied. The obtained results show that these hydrogels have good pH sensitivity which can avoid drug release in stomach, and their swelling kinetics in stimulant intestinal environment follow second-order swelling kinetics equation. The factors influencing the swelling kinetics include the degree of cross-linking and the composition, which may control no release or a little amount release of drug inside the hydrogels in the small intestine by tailoring these factors. The gels are degradable by colonic enzymes and there is a correlativity between the degradation of networks and the swelling degree of the gels, which may trigger the release of drug in the colon. The hydrogels show a great potential for their application in oral colon-specific drug delivery system.
基金Project Supported by Science Foundation of Shanghai MunicipalCommission of Science and Technology (Grant No .02DJ14030)
文摘The thermosensitive poly ( N-isopropylacrylamide ) (PNIPAAm) and poly (N-isopropylacrylamide-co-acrylamide) [ poly (NIPAAm-co-AAm) ] hydrogels with different acrylamide molar percentage are prepared by radiation polymerization using Co^60 γ-ray. Their swelling equilibrium data in the media of deionized water, NaCl aqueous solutions and different pH buffer solutions are determined. It appears that lower critical solution temperature (LCST) of the hydrogels will drop with the increase of ionic strength and increase with the rising of acrylamide content, A semi-empirical formula is set up with the experimental results. Moreover, it also indicates that this copolymer is pH-sensitive, which is similar to the homopolymer of PNIPAAm.
基金supported by Distinguished Young Scholars(21525101)the NSFC(91422302,and 21371037)
文摘OBJECTIVE To explore a novel pH-sensitive fluorescent probe for in vivo tumor imaging.METHODS Zn5 were obtained in 140℃ after mixed with Me OH,water,Zn(NO_3)2·6 H_2O,H4L and trimethylamine.The fluorescence spectra of Zn5 with the same concentration in different pH aqueous solutions were detected.And the stability of Zn5 was investigated by time dependent fluorescence emission spectra of Zn5 in BSA aqueous solution and 5.0% serum solution.Then,the cytotoxicity of Zn5 was detected by MTT assays.To clarify whether a similar fluorescence response occurs in biological organisms,He La cells were pretreated with probe Zn5(0.5 μmol·L^(-1)) and fluorescence imaging were collected for targeting lysosomes in living cells because of lysosomes′ acidic microenvironment.The A375 tumor-bearing mice were used to assess the imaging ability of Zn5 in vivo.Mouse tumor xenografts were established by injection of A375 cells with 2×10~6 cells per flank.Probe(1 μg·g^(-1)) was administered to mice by injection.Images were obtained using IVIS Spectrum CT Imaging System.RESULTS There is a 11-fold intensity increasing as the pH values changing from 8 to 2.The almost unchanged emission intensities suggest Zn5 is stable in both BSA and serum.Zn5 has negligible cytotoxicity for He La,293 T and CHO-K1 cells.Zn5 can selectively display lysosomes in living cells.Both the 2D and 3D images in vivo distinguish the tumor from other tissues with good fluorescence contrast.CONCLUSION The high chemical stability,emission in the Vis/NIR range,pH sensitivity,a pKa located in the tumor pH range,and low toxicity make Zn5 is suitable for application as a pH-sensitive fluorescent probe for bio-imaging.
基金funded by Beijing Natural Science Foundation (Nos.L222109, 3222018)Military Health Care Project(No.22BJZ22)+6 种基金Science Foundation of China University of Petroleum (Nos.2462019QNXZ02, 2462019BJRC007)National Natural Science Foundation of China (Nos.52211530034, 82273236)Guangdong Provincial Basic and Applied Basic Research Foundation (Nos.2022A151522004, 2022A1515220042)Science and Technology Innovation Commission of Shenzhen (Nos.JSGG20210802153410031, JCYJ20220530141609021)Science and Technology Plan of Shenzhen Nanshan District (No.NS016)Discipline Leader Foundation of Huazhong University of Science and Technology Union Shenzhen Hospital (No.YN2021002)Crosswise Project of Daan Gene (No.HXKY2022002)。
文摘Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped CQDs.Lipo/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.
基金financially supported by the National Natural Science Foundation of China(Nos.51622301 and 51573046)Fundamental Research Funds for the Central Universities(Nos.B14018,WD1616010 and 222201717001)
文摘A novel fluorinated triblock copolymer incorporating 2-ethylhexyl methacrylate (EHMA), tert-butyl methacrylate (tBMA) and 1H,1H,2H,2H-perfluorodecyl acrylate (FA) (PEHMA-b-PtBMA-b-PFA) was first synthesized using three successive reversible addition fragmentation chain transfer (RAFT) polymerization and the subsequent hydrolyzing at acidic condition. The as-fabricated triblock copolymer exhibited an interesting morphology evolution from the multi-compartment rod-like structure to spherical structure along with the addition of a selective solution. At the same time, a visible phase separation domain could be seen in the core area due to the existence of fluorocarbon segments. Furthermore, the self- assembly behavior of the triphilic copolymer at different pH was also verified by transmission electron microscopy, as well as the dynamic light scattering. These stimuli-responsive multi-compartment nanostructures may have potential applications in drug delivery.
基金supported by National Key R&D Program of China(no.2017YFA0205600)Guangdong Natural Science Funds for Distinguished Young Scholar(no.2017A030306018)+4 种基金National Natural Science Foundation of China(nos.51922043 and 31771091)Guangdong Provincial Programs(nos.2017ZT07S054 and 2017GC010304)Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(no.2018GZR110102001)the Science and Technology Program of Guangzhou(nos.201902020018 and 201804020060)Fundamental Research Funds for Central Universities.
文摘Robust cytosolic protein delivery requires both efficient protein binding with delivery vehicles and effective protein release after cell internalization.Although a variety of stimuli-responsive carriers have been designed,simultaneously integrating these two functions in one versatile carrier is challenging.Herein,we developed a polyamidoamine(PAMAM)-based polymer with an intracellular pHactuated hydrophobic-to-hydrophilic transition for this purpose.