Showing papers by "Si-Xue Cheng published in 2008"
TL;DR: The results showed the drug-loaded nanoparticles exhibited enhanced cell inhibition because folate targeting increased the cytotoxicity of drug- loaded nanoparticles against folate receptor expressing tumor cells.
254 citations
TL;DR: Different strategies, including physical and chemical strategies, are reviewed for improving the response kinetics of PNIPAAm-based hydrogels based on the factors that are essential to achieve the fast response rate.
Abstract: Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel is one of the most extensively studied thermosensitive hydrogels, it displays a lower critical solution temperature (LCST) at around 33 °C in aqueous solution and undergoes an abrupt thermoreversible change in volume as the external temperature cycles around this critical temperature. The fast response rate of hydrogels is critically important in some applications, such as artificial organs, actuators, and on–off switches. In this article, we review different strategies, including physical and chemical strategies, for improving the response kinetics of PNIPAAm-based hydrogels. Based on the numerous strategies, the factors that are essential to achieve the fast response rate are identified.
153 citations
TL;DR: The in vitro cell viability studies and the in vivo histological studies demonstrated that the hydrogels were non-cytotoxic and biocompatible, which indicated that thehydrogels prepared were promising candidates as injectable scaffolds for tissue engineering applications.
Abstract: Supramolecular hydrogels self-assembled by α-cyclodextrin and methoxypolyethylene glycol−poly(caprolactone)-(dodecanedioic acid)-poly(caprolactone)−methoxypolyethylene glycol (MPEG-PCL-MPEG) triblock polymers were prepared and characterized in vitro and in vivo. The sustained release of dextran-fluorescein isothiocyanate (FITC) from the hydrogels lasted for more than 1 month, which indicated that the hydrogels were promising for controlled drug delivery. ECV304 cells and marrow mesenchymal stem cells (MSC) were encapsulated and cultured in the hydrogels, during which the morphologies of the cells could be kept. The in vitro cell viability studies and the in vivo histological studies demonstrated that the hydrogels were non-cytotoxic and biocompatible, which indicated that the hydrogels prepared were promising candidates as injectable scaffolds for tissue engineering applications.
152 citations
TL;DR: The fluorescence spectroscopy analysis as well as confocal microscopy studies confirmed the DHBC drug carriers could specifically and efficiently bind to cancer cells with pretreatment of biotin-transferrin, suggesting that the multifunctionalized DHBC micelle may be a useful drug carrier for tumor targeting.
143 citations
TL;DR: In this article, diamino cross-linking processes in solution and dense membrane forms were investigated and the cross-linked network in Matrimid/dichloromethane (CH2Cl2) solutions appeared much faster than that in 6FDA-durene/CH2CL2 solutions.
142 citations
TL;DR: In vitro transfections experiments showed that SS-PEI exhibited comparable transfection efficiency, but lower cytotoxicity in comparison with 25kDa PEI, and the RGD peptide was added to disulfide-containing polyethyleneimine/DNA binary complexes to evaluate the influence of RGD addition for the particle size, zeta potential, morphology, and transfectional efficiency.
126 citations
TL;DR: Alginate based microparticle drug delivery systems were prepared for the sustained release of antineoplastic drugs and the effect of the reinforcement conditions on the drug release property of the microparticles was studied, and the optimized concentration of chitosan solution for reinforcement was identified.
112 citations
TL;DR: The data obtained show that the novel hydrogels have the strong desire to respond to external temperature and pH stimuli.
110 citations
TL;DR: A series of thermosensitive ABA type triblock poly(e-caprolactone)-b-poly(N-isopropylacrylamide)-poly(poly(e)-caprolactorone) (PCL-PNIPAAm-PCL) copolymers with different molecular weights were synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization as mentioned in this paper.
Abstract: A series of thermosensitive ABA type triblock poly(e-caprolactone)-b-poly(N-isopropylacrylamide)-b-poly(e-caprolactone) (PCL-PNIPAAm-PCL) copolymers with different molecular weights were synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization The critical micelle concentrations (CMCs) of the resulted four triblock copolymers in aqueous solution were determined to be 338, 398, 355, and 417 mg/L, respectively, by fluorescence spectroscopy using pyrene as a fluorescence probe Optical absorption measurements showed that the lower critical solution temperatures (LCSTs) of the copolymers were 358, 362, 352, and 362 °C, respectively, in distilled water, and 339, 342, 333, 346 °C, respectively, in PBS (pH = 68, I = 01) Transmission electron microscopy (TEM) showed that the self-assembled micelles exhibited a well-defined spherical shape with diameter of around 100 nm The drug-loaded PCL-PNIPAAm-PCL micelles displayed thermosensitive controlled release behaviors © 2008 Wiley Periodicals, Inc J Polym Sci Part A: Polym Chem 46: 3048–3057, 2008
104 citations
TL;DR: The results indicated that the molecular weight of NMC-g-PEI has an important effect on cytotoxicity and transfection activity, and low molecular weight NMC -g- PEI has a good potential as efficient nonviral gene vectors.
102 citations
TL;DR: Cytotoxicity study shows that the AC-PCL-HEMA/AAc copolymer exhibits good biocompatibility.
TL;DR: The drug loading and in vitro drug release properties of the SCL micelles bearing a silica-reinforced PNIPAAm shell showed a much improved entrapment efficiency (EE) as well as a slower release rate which allowed the entrapped molecules to be slowly released over a much longer period of time as compared with pure PNipAAm-b-PMMA micells.
Abstract: Shell cross-linked (SCL) thermoresponsive hybrid micelles consisting of a cross-linked thermoresponsive hybrid hydrophilic shell and a hydrophobic core domain were synthesized from poly(N-isopropylacrylamide-co-3- (trimethoxysilyl)propyl methacrylate)-b-polymethyl methacrylate (P(NIPAAm-co-MPMA)-b-PMMA) amphiphilic block copolymers. Transmission electron microscopy (TEM) images showed that the SCL micelles formed regularly globular nanoparticles. The SCL micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 33 °C, observed by turbidity measurements and dynamic light scattering (DLS). The drug loading and in vitro drug release properties of the SCL micelles bearing a silica-reinforced PNIPAAm shell were further studied, which showed that the SCL micelles exhibited a much improved entrapment efficiency (EE) as well as a slower release rate which allowed the entrapped molecules to be ...
TL;DR: It was found that the resulting polymers were able to form electrostatic complexes with plasmid DNA and did not show apparent cytotoxicity in 293T cells, suggesting great potential for achieving the synergistic effect of drug and gene therapies.
Abstract: A series of amphiphilic cationic methoxy polyethylene glycol-b-poly{N-[3-(dimethylamino)propyl]methacrylamide-co-[2-hydroxylethylmethacrylate-poly(e-caprolactone)]} {MPEG-b-P[NDAPM-co-(HEMA-PCL)]} polymers were synthesized by combining reversible addition–fragmentation chain transfer (RAFT) polymerization and the macromonomer method. The resulting polymers were able to self-assemble into micelles in water with a critical micellar concentration (CMC) in the range of 10–30 mg L−1 and the CMC increased with the decrease in the PCL block content. It was found that the resulting polymers were able to form electrostatic complexes with plasmid DNA. The polymer–DNA complexes did not show apparent cytotoxicity in 293T cells. Importantly, the complexes exhibited good transfection efficiency in 293T cells at certain N/P ratios, while doxorubicin-loaded polymeric micelles also displayed controlled drug release. Besides, confocal microscopy showed that the drug and gene simultaneously carried by the cationic micelles could be delivered into the same cells, suggesting great potential for achieving the synergistic effect of drug and gene therapies.
TL;DR: (Dex-HMDI)-g-PEI with a low molecular weight dextran demonstrates lower cytotoxicity and higher transfection efficiency, and comparing with (Dex-Dextran-hexamethylenediisocyanate-g-polyethylenimines) with a high molecular weightDextran, ( Dex-H MDI) with the similar buffer capability regardless of the different molecular weight of dextrans.
TL;DR: In this article, the in situ chemical gelation of poly(N-isopropylacrylamide-co-hydroxylethyl methacrylate) [P(NIPAAm-Co-HEMA)]-based polymers was demonstrated.
Abstract: The strategy for in situ chemical gelation of poly(N-isopropylacrylamide-co-hydroxylethyl methacrylate) [P(NIPAAm-co-HEMA)]-based polymers was demonstrated. Two types of new P(NIPAAm-co-HEMA) derivatives with alkyne and azide pendant groups, respectively, were prepared. When the solutions of the two derivatives were mixed together, a crosslinking reaction, a type of Huisgen's 1,3-dipolar azide-alkyne cycloaddition, in the presence of Cu(I) catalyst occurs. The morphology, equilibrium swelling ratio, swelling kinetics, and temperature response kinetics of the in situ gelated hydrogels were studied. In comparison with the conventional PNI-PAAm hydrogel, because of the spatial hindrance of polymeric chains, the resulted hydrogels had a macroporous structure as well as a fast shrinking rate. The strategy described here presents a potential alternative to the traditional synthesis techniques for the in situ formation of thermoresponsive hydrogels.
TL;DR: 5-Fluorouracil (5-FU), an anticancer drug, was encapsulated in the nanospheres and vesicles, and in vitro drug release behavior was investigated, and the effect of drug-loading content on the release was studied.
Abstract: A new method was developed to fabricate nanospheres and vesicles as drug carriers. The drug-loaded nanospheres and vesicles were prepared by self-assembly of alginate in aqueous media containing Ca2+ and CO32− ions under very mild conditions. The preparation method did not involve any organic solvent and surfactant and could offer good control over the morphology and the size of self-assemblies. Through adjusting the preparation conditions, nanosized drug-delivery systems with different shapes, that is, nanospheres and vesicles, could be obtained. The morphologies of the drug-delivery systems were observed by transmission electron microscopy (TEM). 5-Fluorouracil (5-FU), an anticancer drug, was encapsulated in the nanospheres and vesicles, and in vitro drug release behavior was investigated. The effect of drug-loading content on the release was studied. The release of 5-FU could be effectively sustained from both drug-loaded nanospheres and vesicles because the presence of CaCO3 in the nanospheres/vesicle...
TL;DR: The results revealed that the transfection efficiency of CMD-g-PEI at the N/P ratios over 30-70 was higher than or comparable to that of the 25 kDa PEI at optimal ratio (N/P = 10).
Abstract: In this study, the low molecular weight branched polyethylenimine (PEI) (800 Da PEI) was grafted to the biodegradable and biocompatible carboxymethyl dextran (CMD) to obtain CMD-g-PEI, and the plasmid DNA was complexed with CMD-g-PEI polycation to form the polyion complex. The acid-base titration profile showed that the CMD-g-PEI had endosomal disruption capacity, and the agarose gel electrophoresis suggested that the CMD-g-PEI could condense DNA efficiently. The transfection efficiency of CMD-g-PEI/DNA complexes was measured by luciferase and green fluorescent protein assay in HEK293 cells. The results revealed that the transfection efficiency of CMD-g-PEI at the N/P ratios over 30–70 was higher than or comparable to that of the 25 kDa PEI at optimal ratio (N/P = 10). The cytotoxicity of CMD-g-PEI as well as 25 kDa PEI was evaluated in NIH3T3 and HEK293 cells, respectively, and it was also found that the cytotoxicity of CMD-g-PEI was much lower than that of 25 kDa PEI. The resulted CMD-g-PEI with high transfection efficiency and low cytotoxicity have promising applications when used as gene vector. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
TL;DR: In this article, a series of star block copolymers poly(l-lactide)-star block-poly(N-isopropylacrylamide-co-N-hydroxymethylacryamide) with different molar feed ratios of NIPAAm and HMAAm were designed and synthesized.
Abstract: A series of star block copolymers poly(l-lactide)-star block-poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide) (PLLA-sb-P(NIPAAm-co-HMAAm)) with different molar feed ratios of NIPAAm and HMAAm were designed and synthesized. An ideal P(NIPAAm-co-HMAAm) (13:1) copolymer was found, which exhibited reversible phase transitions at around 36.8 °C, being close to human physiologic temperature (37 °C). Such a star block copolymer was comprised of a hydrophobic PLLA arm and an average of six hydrophilic P(NIPAAm-co-HMAAm) arms, determined by molecular weight analysis. The amphiphilic PLLA-sb-P(NIPAAm-co-HMAAm) copolymer was capable of self-assembling into nanosized micelles in water, and transmission electron microscopy images showed that the self-assembled nanoparticles were regularly spherical in shape. The anticancer drug methotrexate (MTX) was loaded in the polymeric micelles, and the in vitro release behavior of MTX was investigated. It was found that resulting PLLA-sb-P(NIPAAm-co-HMAAm) micelles showe...
TL;DR: Fluorescence spectroscopy and confocal microscopy studies confirmed that the self-assembled biotinylated micelles can be specifically and efficiently bonded to cancer cells with the administration of biotin-transferrin, suggesting that the multifunctional micells have great potential as drug carriers for tumor targeting chemotherapy.
TL;DR: By adjusting the pH, the molecular interactions of amphiphilic peptide derivatives are tuned, which results in a morphology change, and the results reveal that the amphiphiles with different molecular structures exhibit different self-assembly behavior in response to environmental changes.
Abstract: A series of bioactive amphiphilic peptide derivatives that contain the RGD (Arg-Gly-Asp) sequence have been designed and prepared by the standard solid-phase peptide synthesis (SPPS) technique. The influence of the molecular structure and pH change on the morphology of the amphiphilic peptide derivatives in aqueous solution is investigated. The results reveal that the amphiphilic peptide derivatives with different molecular structures exhibit different self-assembly behavior in response to environmental changes. Furthermore, by adjusting the pH, the molecular interactions of amphiphilic peptide derivatives are tuned, which results in a morphology change.
TL;DR: To overcome the extracellular barriers in gene delivery and direct gene delivery to target tissues, substrate‐mediated transfection has been developed, which sustains the release of naked DNA or vector/DNA complexes, and also supports cell growth.
Abstract: Background
To overcome the extracellular barriers in gene delivery and direct gene delivery to target tissues, substrate-mediated transfection, which sustains the release of naked DNA or vector/DNA complexes, and also supports cell growth, has been developed.
Methods
In the present study, polyamidoamine (PAMAM) dendrimer/DNA complexes encapsulated functional biodegradable polymer films for substrate-mediated gene delivery were prepared. To maintain the activity of DNA during dehydration, the dendrimer/DNA complexes were encapsulated in a water soluble polymer, poly α,β-[N-(2-hydroxyethyl)-L-aspartamide], and then deposited on or sandwiched in functional polymer films with a fast degradation rate to mediate gene transfection. The in vitro gene transfections of pGL3-Luc and pEGFP-C1 plasmids in HEK293 cells mediated by different films were studied. For comparison, the transfection mediated by the film fabricated by conventional linear poly(DL-lactide) was also investigated.
Results
The expression of pGL3-Luc and pEGFP-C1 plasmids could effectively be mediated by the PAMAM/DNA complexes deposited or sandwiched polymer films, with transfection efficiencies comparable to that of solution-based transfections. The cells on the functionalized star poly(DL-lactide) film exhibited much higher gene expression compared to the cells on the conventional linear poly(DL-lactide) film because the fast degradation rate of star poly(DL-lactide) facilitated the access of PAMAM/DNA complexes for the cells seeded on the film. In addition, the films did not exhibit any additional cytotoxicity to the cells during the degradation and transfection.
Conclusions
The fast degrading functional polymer has great potential for localized transfection. Copyright © 2008 John Wiley & Sons, Ltd.
TL;DR: In vivo study showed the self-assembled micelles of Eu(DBM)(3) coordinated P(MMA-co-EIPPMMA)-co-P(NIPAAm- co-NDAPM) copolymer uptaken by the larvae of zebrafish could be easily tracked and be eliminated from the body within several days.
Abstract: An amphiphilic tris(dibenzoylmethanato)europium(III) (Eu(DBM)3) coordinated P(MMA-co- EIPPMMA)-co-P(NIPAAm-co-NDAPM) copolymer was synthesized, which exhibited good biocompatibility and emitted strong red luminescence (MMA, methyl methacrylate; EIPPMMA, 4-(1-ethyl-1H-imidazo(4,5- f)(1,10)phenanthrolin-2-yl)phenyl methacrylate; NIPAAm, N-isopropylacrylamide; NDAPM, (N-(3- dimethylamino)propyl)methacrylamide). The copolymer could self-assemble into micelles of size around 260 nm, and the micelles were thermosensitive at around body temperature. The drug-loaded micelles showed thermosensitive controlled drug release, and the paclitaxel loaded micelles were capable of being internalized intothetumorcells(A549)andexhibitedobviousinhibitiontothegrowthofA549cells.Importantly,invivostudy showed the self-assembled micelles of Eu(DBM)3coordinated P(MMA-co-EIPPMMA)-co-P(NIPAAm-co-NDAPM) copolymer uptaken by the larvae of zebrafish could be easily tracked and be eliminated from the body within several days.
TL;DR: It was found that the transfection efficiency of P(NIPAAm- co-NDAPM)- b-PEI/ DNA complexes was higher than or comparable to that of 25 kDa PEI/DNA complexes at their optimal N/P ratios.
TL;DR: In this article, the authors demonstrated the preparation of temperature-responsive magnetomicelles that consist of a functionalized hexagonal magnetic core, Fe3O4-undecylenic acid, and an amphiphilic surface layer of temperatureresponsive polymer.
TL;DR: An interesting transition from spherical micelles to vesicles, which was time and temperature dependent, was observed for the first time; it is tentatively attributed to the thermal hysteresis of temperature-responsive poly(N-isopropylacrylamide).
TL;DR: Fluorescence spectroscopy analysis as well as confocal laser scanning microscopy was used to confirm that the Tf-conjugated nanogels could specifically bind to A549 tumor cells and could efficiently release the drug inside the cell, suggesting that the NIPAAm-co-PAAc- co-HEMA Nanogels are useful drug carriers for tumor cell targeting.
Abstract: Multifunctional and thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid-co-hydroxyethyl methacrylate) (P(NIPAAm-co-PAAc-co-HEMA)) nanogels were prepared by miniemulsion polymerization. The mean sizes of the nanogels measured by dynamic light scattering (DLS) varied from 120 to 400 nm with an increase in temperature. Transmission electron microscopy (TEM) showed that the nanogels displayed well-dispersed spherical morphology. The nanogels were conjugated by human transferrin (Tf) and the coupling of transferrin molecules with nanogels was verified by UV–vis spectroscopy. The cytotoxicity study indicated that the nanogels did not exhibit apparent cytotoxicity. Fluorescence spectroscopy analysis as well as confocal laser scanning microscopy (CLSM) was used to confirm that the Tf-conjugated nanogels could specifically bind to A549 tumor cells. In addition, the Tf-conjugated nanogels loaded with Doxorubicin (Dox) could efficiently release the drug inside the cell, suggesting that the Tf-conjugated nanogels are useful drug carriers for tumor cell targeting.
TL;DR: The cytotoxicity study indicated P(NIPAAm-co-PAAc) nanogels exhibited a better biocompatibility than both PNIP AAm nanogel and PEI-g-PEI nanogEL although all the three kinds of nanogles did not exhibit apparent cytot toxicity.
Abstract: A series of biocompatible and stimuli-sensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (P(NIPAAm-co-PAAc)) nanogels were synthesized by emulsion polymerization. In addition, polyethyleneimine (PEI) was further grafted to modify the PNIPAAm-based nanogels. The P(NIPAAm-co-PAAc)-g-PEI nanogels exhibited good thermosensitivity as well as pH sensitivity. Transmission electron microscopy (TEM) showed that the P(NIPAAm-co-PAAc)-g-PEI and P(NIPAAm-co-PAAc) nanogels displayed well dispersed spherical morphology. The mean sizes of the nanogels measured by dynamic light scattering (DLS) were from 100 nm to 500 nm at different temperatures. The cytotoxicity study indicated P(NIPAAm-co-PAAc) nanogels exhibited a better biocompatibility than both PNIPAAm nanogel and P(NIPAAm-co-PAAc)-g-PEI nanogel although all the three kinds of nanogels did not exhibit apparent cytotoxicity. The drug-loaded nanogels, especially the PEI-grafted nanogels, showed temperature-trigged controlled release behaviors, indicating the potential applications as an intelligent drug delivery system.
TL;DR: A series of polycarbonate copolymers were synthesized by the ring-opening bulk polymerization of 2-phenyl-5,5-bis(hydroxymethyl) trimethylene carbonate (PTC) with tin(II) 2-ethylhexanoate and aluminum isopropoxide as initiators as mentioned in this paper.
Abstract: A series of polycarbonate copolymers were synthesized by the ring-opening bulk polymerization of 2-phenyl-5,5-bis(hydroxymethyl) trimethylene carbonate (PTC) and 5,5-dimethyl trimethylene carbonate (DTC) with tin(II) 2-ethylhexanoate and aluminum isopropoxide as initiators. The copolymers obtained were characterized by 1 H-NMR, Fourier transform infrared, and ultraviolet. The influence of the molar ratio of the monomers, the initiators, and their concentrations, the reaction time, and the reaction temperature on the copolymerization was also studied. The copolymerization of monomers DTC and PTC was a nonideal copolymerization, and the copolymerization reactivity ratio of the monomer DTC was higher than that of PTC in the copolymerization process. In vitro release profiles of fluorouracil from the copolymers showed that the copolymer had a steady drug-release rate and good controlled-release property.
TL;DR: Based on the specific physicochemical property of the graft copolymers, submicron sized microsphere drug delivery systems were prepared by a very convenient “ultrasonic dispersion method”, which did not involve toxic organic solvents.
TL;DR: An effective strategy was developed and demonstrated to improve the properties of thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel by using diethyl ether as a precipitation agent during the polymerization/crosslinking.
Abstract: An effective strategy was developed and demonstrated to improve the properties of thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel by using diethyl ether as a precipitation agent during the polymerization/crosslinking. Results reveal that the modified PNIPAAm hydrogels have the heterogeneous network structures and decreased LCSTs in a comparison with the normal PNIPAAm hydrogel. The modified PNIPAAm hydrogels also exhibit significantly improved sensitive properties, including fast response and stable, rapid, large magnitude oscillatory shrinking-swelling upon temperature cycles around lower critical solution temperature. In addition, fish DNA, used as a model drug, is loaded into the modified PNIPAAm hydrogels, the controlled release behaviors of the drug loaded hydrogels at different temperatures (22 and 37 degrees C) are further examined.