RSC Advances
·
2016
·Vol. 6
·期 34
·28331-28342
·
IF 3.289
Lu Wang,Xi Xie,Di Liu,Xiao-Bin Fang,Peng Li,Jian-Bo Wan,Cheng-Wei He,Mei-Wan Chen
Reduction-sensitive micelles with crosslinked cores were developed to load the lipophilic chemotherapeutic drug docetaxel (DTX) in order to overcome the issues of toxicity, water insolubility, and rapid metabolism of DTX. These DTX-loaded micelles (MM(DTX/Crosslink)) provide efficient incorporation and sustained release of DTX. Using independently synthesized LA–PLGA–TPGS and DSPE–PEG polymers as vehicles, MM(DTX/Crosslink) was found to be reduction-responsive, and possessed desirable drug entrapment efficiency (84.17 ± 1.15%) and drug loading efficiency (6.21 ± 0.07%). The MM(DTX/Crosslink) quickly dissociated under reduction conditions that mimicked the reductive intracellular environment, suggesting that it can rapidly release the encapsulated DTX in vitro. Furthermore, to target MM(DTX/Crosslink) to tumors for cancer therapy, iRGD was conjugated to the surface of MM(DTX/Crosslink). The iRGD-MM(DTX/Crosslink) micelles significantly increased the cellular uptake of DTX and inhibited cell proliferation, compared to the micelles without iRGD modification. Moreover, the iRGD-MM(DTX/Crosslink) micelles presented enhanced antitumor effects based on the analyses of apoptosis and cell cycle arrest. The micelles developed in this work may constitute a stable, efficient, and powerful system to deliver DTX into cancer cells.
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EUROPEAN POLYMER JOURNAL
·
2016
·
IF 3.485
Tao Chen,Xiaohua Han,Zhi Peng,Aihua Li,Jingquan Liu
7, 8-Dihydroxyflavone (7, 8-DHF) is an effective drug for the treatment of Parkinson’s disease. However, its application is heavily limited by its poor water solubility. To improve its hydrophilicity, biocompatible poly (ethylene glycol)acrylate (PEG-A) was grafted onto 7, 8-DHF via in situ reversible addition-fragmentation chain transfer (RAFT) polymerization, forming a kind of a drug/polymer composite, DHF/PPEG-A. It was found that the solubility of DHF/PPEG-A was significantly improved by 78 times compared to the unmodified precursor. Impressively, both the cytotoxicity and the drug efficacy of the synthesized DHF/PPEG-A just slightly decreased compared with the unmodified 7, 8-DHF. Moreover, the drug efficacy of DHF/PPEG-A can be regained by the hydrolysis in the presence of the esterase D due to the decomposition to 7, 8-DHF in body. This dramatical improvement of the water solubility of DHF/PPEG-A and the insignificant compromise of its drug cytotoxicity could envision extensive practical clinical administration of 7, 8-DHF for enhanced drug efficacy.
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Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 7
·1284-1295
·
IF 4.872
Min Tang,Haiqing Dong,Yongyong Li,Tianbin Ren
Dendrimer catiomers like dendrigraft poly-L-lysine (DGL) have been very popular vectors for gene delivery recently; however, they generally suffer from serious cytotoxicity for high density of positive charge. PEGylated DGL engineered using the PEG cleavable mechanism (DGL(R)-SS-mPEG) was first developed as a non-viral gene vector for cancer intervention. Cleavable PEGylation of the DGL catiomer in tumor relevant glutathione (GSH) conditions enables us to dramatically decrease the cytotoxicity as well as to promote the intracellular release and expression of the genetic payload. Like DGL, DGL(R)-SS-mPEG is capable of efficiently complexing with plasmid DNA (pDNA) to afford homogeneous compact nano-complexes. Those gene carrying nanostructures could be stably dispersed in the regular serum medium without GSH, but with fast PEG dis-assembly if subject to 10 mM GSH. Compared with the non-cleavable counterpart, PEG-cleavable dendrigraft poly-L-lysine exhibited significantly higher enhanced green fluorescence protein (EGFP) expression against 293T cells. By using small interfering RNA (siRNA-VEGF) as the therapeutic gene payload, the complex nanoparticles demonstrated the pronounced inhibition effect on cell growth in vitro and tumor growth in vivo. The promising results revealed a universal strategy to balance disadvantages and advantages of dendrimer catiomers for future non-viral gene delivery vector.
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Polymer Chemistry
·
2015
·Vol. 6
·期 13
·2445-2456
·
IF 5.52
Minghui Xu,Junmin Qian,Aili Suo,Ting Liu,Xuefeng Liu,Hongjie Wang
To enhance the therapeutic efficacy of doxorubicin (DOX) to breast cancer cells, a multifunctional triblock copolymer, poly(ethylene glycol)-block-poly(L-glutamic acid γ-hydrazide)-block-polyethylenimine (PEG-b-PGAH-b-PEI) having a cleavable disulfide linkage between blocks, was developed as a vehicle for targeted co-delivery of DOX and P-glycoprotein (P-gp) siRNA into MCF-7/ADR cells. The PGAH blocks were used to chemically conjugate DOX molecules via hydrazone bonds, while the PEI blocks could complex siRNA through electrostatic interactions. A tumor-targeting agent, folic acid (FA), was attached to the distal ends of the PEG blocks to specifically bind to the folate receptors overexpressed in MCF-7/ADR cells. The DOX-conjugated copolymer would self-assemble in aqueous solutions into cationic nanomicelles, which could condense siRNA to form nanomicelleplexes with an average particle size of ∼194 nm and a positive zeta potential of >+10 mV. The nanomicelleplexes exhibited sustained drug release profiles, and the release rates of DOX and siRNA from the nanomicelleplexes in a reductive acidic environment (pH 5.0 + 10 mM glutathione) were much faster than those under physiological conditions (pH 7.4). FA-decorated nanomicelleplexes were more efficiently internalized by MCF-7/ADR cells via folate-receptor-mediated endocytosis and exhibited a higher cytotoxic effect on MCF-7/ADR cells in comparison with FA-undecorated nanomicelleplexes. Furthermore, the synergistic effects of DOX and P-gp siRNA in inhibiting cell proliferation and inducing apoptosis in MCF-7/ADR cells were achieved by the FA-targeted co-delivery system. The triblock copolymer itself had a low cytotoxicity. These results indicate that the triblock copolymer could serve as an ideal tumor-targeting vehicle for simultaneous delivery of drugs and siRNA in breast cancer therapy.
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Polymers
·
2025
·Vol. 17
·期 5
·574
·
IF 4.9
Lin Fu,Hengxin Ren,Chaoxing Wang,Yaxin Zhao,Bohang Zou,Xiangyu Zhang
Polymer-based drug-controlled release systems offer greater efficacy and potency than conventional therapies. However, prominent drug side effects, lower circulation, and low drug loading capabilities limit their application range. In this work, the combination of Simvastatin (SIV) and Carvacrol (CAV) into PEG-PLGA microspheres (SIV-CAV-PP-MS) was achieved via an emulsification-solvent evaporation technique, resulting in microspheres characterized by high encapsulation efficiency and reduced particle size. In vitro studies demonstrated that the cumulative drug release increased with higher SIV and CAV levels in the release medium, reaching 88.91% and 89.35% at 25 days. Pharmacokinetic analysis revealed that the concentrations of SIV and CAV reached their maximum levels at approximately seven days in the SIV-CAV-PP-MS group, which indicates that using PEG-PLGA as a carrier significantly delays drug release. In vivo, evaluation demonstrated that the SIV-CAV-PP-MS high-dose group and positive drug control group showed reductions in low-density lipoprotein cholesterol levels by 0.39-fold and 0.36-fold compared to the Hyperlipidemia model group, and the addition of CAV significantly enhanced the lipid-lowering effects of SIV. Histological examinations indicated that the SIV-CAV-PP-MS medium-dose group displayed histological features more closely resembling those of normal mice compared to the Simvastatin control group, with a well-organized hepatocyte structure, a significant reduction in lipids, and improved liver health. The prepared polymeric microsphere utilizing SIV and SAV will be a promising dosage form for hyperlipidemia disease patients, with superior lipid-lowering efficacy and improved patient compliance.
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MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Le-Yan Feng,Zhenhua Tang,Nuan Xu,Jiaxin Huang,Yan-Ping Jiang,Xin-Gui Tang,You Zeng,Shang-Xian Chen
Antibiotics play an essential function in treating various diseases. However, their overuse has led to water pollution and food safety issues. This work discusses a highly sensitive ratiometric fluorescent flexible sensor based on multifunctional 4-MU@ZIF-8@PLA-PEG composite film prepared using a low-toxicity, eco-friendly and self-assembly method. The sensor combines the luminescent properties and structural tunability of ZIF-based composites with the processability and flexibility of polymers. The 4-MU@ZIF-8@PLA-PEG sensor can detect tetracycline (TC), oxytetracycline (OTC), chlortetracycline hydrochloride (CTC⋅HCl), and doxycycline hydrochloride (DOX⋅HCl) with dual-emission ratiometric fluorescence, exhibiting a visible color change from blue to yellow, with detection limits of 0.058 nM, 16.806 nM, 2.113 nM and 20.510 nM, respectively. The fluorescence characteristics exhibit excellent linear relationships with TC detection in tap water and milk, and show inhibition rates of 87.27 % and 76.61 % against E. coli and S. aureus . With its antibacterial activity, visual detection, high sensitivity, and short detection time, this sensor has significant potential for detecting antibiotics in aquatic environments and food safety applications.
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LANGMUIR
·
2025
·
IF 3.9
Jingwen Zhao,Peng Zhu,Huapeng Zhang
A ternary polymer–solvent mixture has already been proposed to prepare surface porous films. However, the uncertainty of the formation mechanism of surface porous films and the multitude of influencing factors with unclear priorities lead to the failure to promote this method. Here, a surface-porous polystyrene (PS) film with a pore size of 0.6 μm was successfully prepared from a ternary PS/poly(ethylene glycol)–tetrahydrofuran (PEG–THF) mixture, using ultrasonic dissolution to provide a dispersion effect. The total polymer concentration, PEG molecular weight, PS/PEG mass ratio, dissolution temperature, and evaporation temperature can help to optimize surface porous structures. Based on the rheological behavior of the ternary PS/PEG–THF mixture and comparative experiments with the traditional dissolution method, the formation mechanism of surface porous structures has been revealed. After dissolution, the ternary mixture should be viewed as a two-phase dispersion, emphasizing the dispersion effect of the dissolution process. The formation of surface pores is derived from the transportation, arrangement, and evaporation of dispersed PEG–THF domains. Thus, the preparation of high-quality surface porous films through a ternary polymer dispersion mainly requires attention to two points: the dissolution and dispersion method and the solvent selection. To obtain submicron surface porous films, a synergistic effect of the two is required.
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Nanoscale Advances
·
2025
·
IF 4.6
Mengting Tong,Guangpeng Chen,Yong Dong,Yubin Pan,Yanan Xue,Da Li
Despite the progress made in novel immunotherapy for hepatocellular carcinoma (HCC), drug resistance remains a challenging problem. In this study, we developed a stepwise nanodrug delivery system, known as Au-SS-PEG/Sor/ATP aptamer /LHRH-MPG ΔNLS , to adapt to the high concentrations of glutathione (GSH) and adenine nucleoside triphosphate/adenosines (ATP/ADO) found in cancer cells and the tumor microenvironment (TME). This system utilizes novel Au nanoclusters conjugated with disulfide-linked PEG as vectors to transport sorafenib (Sor) and an ATP-binding nucleic acid aptamer (ATP apt ). It can enter HCC cells through luteinizing hormone-releasing hormone (LHRH)-MPG ΔNLS (LM). Within the cells, the disulfide bonds of the nanoclusters are cleaved by the high levels of GSH, leading to the release of Sor/ATPapt. This release can be further triggered by ATP/ADO, resulting in a stepwise drug release mechanism. Furthermore, this nanodrug system has exhibited the ability to overcome αPD-1 resistance in HCC tumors. In summary, our novel drug delivery system demonstrates a dramatic anti-HCC effect and holds great potential for treating HCC patients. Synthesis and mechanistic illustration of Au-SS-PEG/Sor/ATP apt /LM nanoclusters for the treatment of hepatocellular carcinoma (HCC).
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Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Chunzhi Huang,Jilian Wu,Wei Jiang,Ruiling Liu,Zhonghao Li,Yuxia Luan
Graphene oxide (GO) has shown great potential in drug delivery. However, the aqueous stability, non-specific drug release and slow release rate are major problems of the GO-based drug delivery system. Herein, we for the first time integrate the dispersant, stabilizing agent and active targeting carrier into a novel drug delivery system based on GO/PP-SS-DOX nanohybrids. The redox-sensitive PP-SS-DOX prodrug was obtained by conjugating mPEG-PLGA (PP) with doxorubicin (DOX) via disulfide bond. PEG-FA provided active targeting property for the constructed drug delivery system, GO/PP-SS-DOX/PEG-FA. In this demonstrated system, PP-SS-DOX markedly increases the stability in physiological solutions of GO and guarantees the DOX release in the reductive environment (cancerous cells). And PEG-FA helps target to cancerous tissues and induces FR-mediated endocytosis. In vitro drug release exhibited the obvious reductive sensitivity and the cumulative release amount was up to 90%, while 40% in previous reports within 72 h. The in vitro cytotoxicity of targeting nanohybrids was significantly cytotoxic than that of non-targeting nanohybrids. In vivo results displayed that the as-prepared targeting nanohybrids showed efficacious antitumor effect while it had nearly no systemic adverse toxicity on B16 tumor-bearing mice. Therefore, the in vitro and in vivo results indicate that our constructed GO/PP-SS-DOX/PEG-FA drug delivery system is a promising carrier in cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
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ACS Applied Materials & Interfaces
·
2026
·Vol. 18
·期 30
·40554-40565
·
IF 7.8
Yan Lan-Xi,Zhang Jie,Chen Xiao-Hu,Cao Yu-Tao,Zhao Qing,Wu Gang,Chen Si-Chong,Wang Yu-Zhong
Tissue patches have gained widespread attention for their ability to rapidly and effectively close tissue wounds. Nevertheless, maintaining robust adhesive strength under physiological conditions remains a significant challenge for current tissue adhesion materials. Herein, a tissue patch material based on a poly( p -dioxanone)- co -poly(ethylene glycol) (PPDO- co -PEG) copolymer is reported. This copolymer is engineered to exhibit a rigid-to-flexible transition property, with N -hydroxysuccinimide (NHS) groups grafted onto its backbone as adhesive functional moieties. The semi-crystalline structure of the PPDO segments enhances cohesive strength, while PEG segments provide segmental mobility under physiological conditions, enabling NHS to penetrate irregular tissue interfaces and react with surface primary amine groups. Therefore, the patch exhibits excellent tissue adhesion performance, with dry and wet adhesive strength of 2.59 MPa and 189.6 kPa, respectively. Furthermore, the patch has the potential for multifunctional applications, such as effectively sealing wounds in multiple organs with outstanding pressure-resistant stability (326 mmHg), while also offering rapid hemostasis and accelerated tissue healing. In summary, this study presents a feasible design strategy for flexible, high-adhesion tissue patches, which show promising potential for clinical applications in wound management and tissue repair.
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BIOMACROMOLECULES
·
2025
·
IF 5.4
Deqing Zhao,Jingpeng He,Yaling Zhao,Kaibin Ma,Yang Xu,Qinqin Xia,Xinglin Xiong,Xuan Tang,Qingyi Zhao,Rongge Wang
Maximizing the extraction and valorization of highly reactive lignin from lignocellulosic biomass is crucial for lignin-first biorefining. However, achieving high yield, superior purity, and structural preservation simultaneously is challenging. Herein, we developed a Lewis acid-catalyzed deep eutectic solvent (DES) system employing ferric chloride (FeCl3) coordinated with polyethylene glycol (PEG) to selectively extract structurally intact lignin. The engineered DES system exhibited outstanding performance, achieving a lignin yield of 32.9% with a purity of 96.2%. Structural analysis indicated that the extracted lignin retained 53.21 β-O-4 linkages per 100 aromatic units, closely approximating the native structure of cellulolytic enzyme lignin (CEL: 58.53 β-O-4/100 Ar). The identification of characteristic β′-O-4 linkages verified that PEG grafting at the Cα position effectively inhibited lignin condensation. Theoretical calculations further confirmed that FeCl3 enhanced the hydrogen-bonding capacity of the ternary DES with lignin, thereby aiding lignin dissociation and improving separation efficiency. This work provides valuable insights into upgrading lignin fractionation for lignin valorization.
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EUROPEAN POLYMER JOURNAL
·
2020
·
IF 3.862
Zhonghan Feng,Huining Wang,Maosheng Liu,Tao Chen,Yan Liu,Wenying Xu,Haiyan Wang,Jingquan Liu
Despite the fact that mitoxantrone (MTX) is an effective prescription drug for cancer therapy, its poor water solubility is a great challenge that limits its practical applications. Herein, to overcome this shortcoming, a drug/polymer conjugate of MTX with poly (ethyleneglycol) acrylate (PEG-A) (MTX/PPEG-A) was developed via in situ reversible addition-fragmentation chain transfer (RAFT) polymerization. Impressively, the MTX/PPEG-A conjugate shows highly improved water solubility, which is about 550% that of the unmodified MTX. The synthesized MTX/PPEG-A conjugate drug efficacy can be maintained and cytotoxicity reduced slightly compared with the unmodified MTX. In addition, the MTX/PPEG-A can be hydrolyzed by the esterase into pristine MTX with restored drug efficacy in vivo. All in all, the significant improvement of the water solubility and the slightly improved biocompatibility of MTX/PPEG-A will be well-suited for the administration and delivery of anti-cancer drugs in cancer therapy.
研究领域:
药学
·
聚合物化学
·
癌症研究
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