RSC Advances
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2016
·Vol. 6
·期 28
·23693-23701
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IF 3.289
Jiulong Zhang,Kang Chen,Ying Ding,Xiu Xin,Wenpan Li,Mengjun Zhang,Haiyang Hu,Mingxi Qiao,Xiuli Zhao,Dawei Chen
pH-Sensitive copolymers have been widely used in drug delivery systems to selectively enhance drug release at tumor sites. Herein, dextran (DX) was conjugated with poly(lactide-co-glycolide) (PLGA) and histidine (His) to prepare a pH-responsive nanocarrier, dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) micelles, for the delivery of antitumor drugs. Different grafting ratio HDP micelles were synthesized and prepared successfully and confirmed by the critical micelle concentration (CMC) and particle size distribution (PSD). In vitro drug release showed that the release behaviour of paclitaxel (PTX) loaded HDP micelles was pH-dependent. All blank micelles were nontoxic in the in vitro cytotoxicity assay. In an MTT assay, PTX-loaded HDP micelles with medium grafting ratios (MHDP) showed the highest cytotoxicity against MCF-7 cells. Cellular uptake experiments revealed that these pH-sensitive micelles could be taken up effectively and PTX could be delivered into the cytoplasm to reach the antitumor effect. NIR fluorescence imaging experiments demonstrated that HDP micelles could specifically accumulate in tumor sites via enhancing the permeability and retention (EPR) effect to reduce their systematic toxicity. In vivo antitumor activities showed that HDP micelles could effectively inhibit tumor growth and prolong survival time compared with free PTX solution. These results confirm that the biocompatible pH-responsive HDP micelles are a novel nanocarrier for the intracellular delivery of PTX.
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MOLECULAR PHARMACEUTICS
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2016
·
IF 4.342
Kun Tian,Xu Jia,Xubo Zhao,Peng Liu
Anticancer drugs cause severe side effects on normal tissues and organs due to their nonspecific delivery. Thus, tumor-targeting delivery of anticancer drugs remains a serious challenge in chemotherapy. Here a facile strategy was established for the pH/reductant dual-responsive core-cross-linked (CCL) micelles for tumor-targeted delivery of anticancer drug, via in situ atom transfer radical polymerization (ATRP). In the in vitro controlled release experiments with doxorubicin (DOX) as a model drug, the premature drug leakage rate was only 13.4% in the physiological medium within 36 h, while the cumulative release rate in the stimulated tumor microenvironment reached 78.7%, demonstrating the excellent tumor microenvironment responsive controlled release behavior upon acidic medium with high GSH level. As a folate receptor (FR) mediated targeting drug delivery system (DDS), the micelles showed excellent cytocompatibility, and enhanced anticancer efficiency after loading of DOX, compared with free DOX.
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CHEMICAL ENGINEERING JOURNAL
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2022
·
IF 16.744
Yan Du,Chunlei Shan,Yuchan You,Minjiang Chen,Luwen Zhu,Gaofeng Shu,Gang Han,Liming Wu,Jiansong Ji,Hong Yu,Yongzhong Du
Lenvatinib (LEN) combined with immune checkpoint PD-1 blockade is among the most effective treatment strategies for advanced hepatocellular carcinoma (HCC) and has been deemed a breakthrough therapy by the Food and Drug Administration. However, this combined strategy is associated with disadvantages such as non-tumor targeted aggregation and low oral bioavailability after long-term administration of LEN, and some patients show poor responses to immunotherapy as well. To overcome these drawbacks, SP94 peptide-modified thermal-sensitive micelles (SP94-poly(ethylene glycol)-poly(acrylamide- co -acrylonitrile, SP94-PEG-p(AAm- co -AN)) with an upper critical solution temperature (UCST) of 43 °C were designed. The micelles were further co-loaded with LEN and IR-1061-Acridine (IR-1061-AcD) to simultaneously achieve small molecule targeted drug, photothermal and photodynamic therapy for HCC under the guidance of near-infrared second-region (NIR-II) fluorescence imaging. After intravenous injection, the co-loaded micelles (SP94-PEG-p(AAm- co -AN)/LEN/IR-1061-AcD, SPLI) showed greater accumulation at tumor sites because SP94 has a high affinity for glucoregulatory protein 78 (GRP78), which is overexpressed on HCC cells. Given these HCC-targeted effects, SPLI appeared useful for NIR-II fluorescence imaging, enabling real-time tumor monitoring and surgical resection. In addition, SPLI could extensively induce immunogenic cell death in tumors, resulting in beneficial systemic immune responses. When further combined with anti-PD-1 immunotherapy, SPLI displayed a superior potential in suppressing tumor growth and metastasis while avoiding immune inhibition. Taken together, our study suggests that the aforementioned combinational strategy could serve as a desired multifunctional approach for HCC management.
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CHEMICAL ENGINEERING JOURNAL
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2021
·
IF 13.273
Maohu Chen,Bo Qiu,Zhanlin Zhang,Shuang Xie,Yuan Liu,Tian Xia,Xiaohong Li
Major challenges remain in combat with the inevitable rise of intrinsic resistance to antibiotics and biofilm formation. Herein, we explore host–guest self-assembled micelles for light-triggered and stimuli-responsive release of antibiotics and β-lactamase inhibitors to combat biofilms derived from methicillin-resistant Staphylococcus aureus (MRSA). β-Cyclodextrin-capped phenylboronic acid-tetraphenylethylene (PBA-TPE) conjugates are coupled with ampicillin (Amp) via reactive oxygen species (ROS)-cleavable thioketal linkers to obtain cd-PTTA prodrug. Adamantane-capped poly(ethylene glycol)-poly(ε-caprolactone) (PECL-ad) amphiphilic copolymers are linked with cd-PTTA via host–guest complexation and simultaneously self-assembled into PECL@PTTA micelles. The digestion of poly(ε-caprolactone) segments by bacterial lipase destructs micelles and the aggregation-induced emission feature of cd-PTTA leads to ROS generation after light illumination. The produced ROS destroys biofilms and breaks thioketal linkers to release Amp antibiotics, while the pH-responsive removal of β-cyclodextrin activates the PBA β-lactamase inhibitors, affording synergistic actions on MRSA. The light illumination and intrinsic signals of acidic pH and lipase display interactive promotions of Amp release, micelle destabilization, and β-lactamase inhibition. Compared to those of cd-PTTA, the PECL@PTTA micelle treatment under light exposure shows sustained growth inhibition of planktonic MSRA, 2-fold higher elimination rate of biofilms, and 28-fold lower number of live MRSA embedded in biofilms. In an MRSA subcutaneous infection model, the micelle treatment with light exposure could eradicate bacteria and a complete wound closure was observed with normal re-epithelialization and skin morphology. Thus this strategy enables synchronous release of antibiotics and activation of β-lactamase inhibitors for photodynamic destruction of biofilms and restoration of the antibiotic activity to resistant bacteria embedded.
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TALANTA
·
2020
·
IF 5.339
Jing Chen,Yuzhi Wang,Xiaoxiao Wei,Ziwei Liu,Fangting Xu,Heqiong Li,Xiyan He
As mixtures, deep eutectic solvent (DES) is designability. By adjusting the long alkyl chain hydrogen bond acceptors (HBAs) or hydrogen bond donors (HBDs), the DES displays surfactant characteristics and can form micelles . Hence, a novel, simple, facile and green natural organic acids capped copper nanoclusters (Aci-CuNCs) was synthesized and the spectrum behavior of Aci-CuNCs in DES micelles was researched. It was found that the surfactant-like DES can form micellar co-aggregation with Aci-CuNCs, resulting in the fluorescence (FL) intensive of Aci-CuNCs increase. Corresponding performance of spectral properties of Aci-CuNCs in DES medium were systematically studied by fourier transform infrared spectrometer, 3D FL spectroscopy, FL emission/excitation spectra, ultraviolet absorption spectroscopy . In the mechanism exploration part, on the one hand, the existence of micellar co-aggregation was confirmed by the conductivity , the mass effect of DES, dynamic light scattering and transmission electron microscopy . On the other hand, the influence of different kinds of DESs (types of HBAs/HBDs, molar ratio) and some possible factors (ionic strength and temperature) were discussed in detail to investigate the main driving forces for the formation of micellar co-aggregates. The results of mechanism exploration prove that the long alkyl chain of DES is amphiphilic which can form micellar co-aggregation with Aci-CuNCs through hydrogen bonding . The DES micelle provides Aci-CuNCs with a relatively stable and closed micro-environment which can effectively prevent collisions with water molecules and weakening of fluorescence intensity . On the basic of the above research, a “turn-off” fluorimetric method based on Aci-CuNCs in DES medium was applied for the determination of Fe 3+ . Under the optimum conditions, the assay worked in the Fe 3+ concentration ranges from 1 to -20 μM and had a detection limit of 0.0374 μM. Method validation study illustrates the proposed system can provide a good accuracy, repeatability and stability conditions. Furthermore, the real sample analysis result demonstrates that no obvious matrix effect is found. As a consequence, the FL assays (Aci-CuNCs-based DES) composed of natural organic acid capped CuNCs and green solvent DES provides a simple, gentle and environmentally friendly method for the detection of iron ions .
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高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Yanqiu Zhang,Lianjun Peng,Jiahui Chu,Ming Zhang,Lizhu Sun,Bin Zhong,Qiyong Wu
Background Co-delivery all-trans-retinoic acid (ATRA) and paclitaxel (PTX) is an effective strategy for cancer therapy. However, in many previous reported ATRA conjugated co-delivery systems, the ATRA was released slower than PTX, and the total drug release of ATRA far lower than that of PTX.Purpose We designed and prepared a pH and redox dual responsive drug delivery system (DA-ss-NPs) co-delivery ATRA and PTX for cancer therapy. The surface charge of DA-ss-NPs could change from negative to positive under tumor slightly acidic microenvironment, and both drugs could be quickly released from DA-ss-NPs under intracellular high concentration of glutathione (GSH).Methods The DA-ss-NPs were constructed by encapsulating PTX into the hydrophobic core of the polymer micelles, in which the polymer was synthesized by conjugating ATRA and 2,3-Dimethylmalefic anhydride (DMA) on side chains of Cystamine dihydrochloride (Cys) modified PEG-b-PAsp (named DA-ss-NPs). The surface charge of DA-ss-NPs under different pH conditions were detected. And the drug release was also measured under different concentration of GSH. The therapeutic effect of DA-ss-NPs were investigated in Human lung cancer A549 cells and A549 tumor-bearing mice.Results The zeta potential of DA-ss-NPs was -16.3 mV at pH 7.4, and which changed to 16 mV at pH 6.5. Cell uptake experiment showed that more DA-ss-NPs were internalized by A549 cells at pH 6.5 than that at pH 7.4. In addition, in presence of 10 mM GSH at pH 7.4, about 75%-85% ATRA was released from DA-ss-NPs within 48 h; but less than 20% ATRA was released without GSH. In vivo antitumor efficiency showed that the DA-ss-NPs could affectively inhibite the tumor in compared with control groups.Conclusion The charge-reversal and GSH-responsive DA-ss-NPs provide an excellent platform for potential tumor therapy.
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PLoS One
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2014
·Vol. 9
·期 10
·e110155
·
IF 3.534
Zhihu Yan,Caili Dai,Haishun Feng,Yifei Liu,Shilu Wang
The viscoelastic properties of worm-like micelles formed by mixing the cationic surfactant N -hexadecyl- N -methylpiperidinium bromide (C 16 MDB) with the anionic surfactant sodium laurate (SL) in aqueous solutions were investigated using rheological measurements. The effects of sodium laurate and temperature on the worm-like micelles and the mechanism of the observed shear thinning phenomenon and pseudoplastic behavior were systematically investigated. Additionally, cryogenic transmission electron microscopy images further ascertained existence of entangled worm-like micelles.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2017
·Vol. 135
·期 9
·45732
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IF 1.86
Xiangke Sun,Xue Liu,Chenglong Li,Yuandou Wang,Li Liu,Feng Su,Suming Li
A series of poly(ɛ-caprolactone)–poly(ethylene glycol) (PCL-PEG) and poly(ɛ-caprolactone/glycolide)–poly(ethylene glycol) [P(CL/GA)-PEG] diblock copolymers were prepared by ring-opening polymerization of ɛ-caprolactone or a mixture of ɛ-caprolactone and glycolide using monomethoxy PEG (mPEG) as macroinitiator and Sn(Oct) 2 as catalyst. The resulting copolymers were characterized using 1 H-NMR, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Copolymer micelles were prepared using the nanoprecipitation method. The morphology of the micelles was spherical or worm-like as revealed by transmission electron microscopy, depending on the copolymer composition and the length of the hydrophobic block. Introduction of the glycolide component, even in small amounts (CL/GA = 10), disrupted the chain structure and led to the formation of spherical micelles. Interestingly, the micelle size decreased with the encapsulation of paclitaxel. Micelles prepared from mPEG5000-derived copolymers exhibited better drug loading properties and slower drug release than those from mPEG2000-derived copolymers. Drug release was faster for copolymers with shorter PCL blocks than for those with longer PCL chains. The introduction of glycolide moieties enhanced drug release, but the overall release rate did not exceed 10% in 30 days. In contrast, drug release was enhanced in acidic media. Therefore, these bioresorbable micelles and especially P(CL/GA)-PEG micelles with excellent stability, high drug loading content, and prolonged drug release could be promising for applications as drug carriers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 45732.
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Acta Biomaterialia
·
2017
·
IF 6.319
Yanan Kang,Lu Lu,Jinshuai Lan,Yue Ding,Jing Yang,Yong Zhang,Yuan Zhao,Tong Zhang,Rodney J.Y. Ho
A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers , which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy , flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer. Statement of Significance The PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere®, indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin , methotrexate and other drugs with carboxy groups in their structure.
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MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2016
·Vol. 217
·期 16
·1851-1859
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IF 2.495
Rui Qi,Yong Jin,Xinfeng Cheng,Hanping Li,Shuangquan Lai,Xiaopeng Sun
Herein, a novel coil-rod-coil triblock copolymer with the coil blocks composed of poly(ethylene glycol) methyl ether and the rigid midterm block alternatively connected with isophorone diisocyanate and isophorone diamine is developed. The triblock copolymer can self-assemble into ellipsoidal micelles in 1-methyl-2-pyrrolidinone. After the addition of a second coil-selective solvent (water) to the micellar solutions, these ellipsoidal micelles can further transform into chain-like nanostructures. The self-assembly behavior is highly influenced by the additional order of the solvents, which is considerably due to the impacts of the hydrogen-bonding urea groups and rigid motifs. The transition of the ellipsoidal micelles to chain-like nanostructures is governed by the water molar fractions. The sizes of the chain-like nanostructures increase first and then decrease with the growth of the water molar fractions in the mixed solutions.
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International Journal of Nanomedicine
·
2023
·
IF 8
Yue Yang,Yunjian Li,Kai Chen,Ling Zhang,Sen Qiao,Guoxin Tan,Fen Chen,Weisan Pan
Purpose Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.Methods The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.Results The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.Conclusion Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.
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JOURNAL OF ORGANOMETALLIC CHEMISTRY
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2021
·
IF 2.369
Xueyi Chang,Qun Luo,Yongfu Qiu,Zhiyu Cheng,Guiping Tan,Tao Guan,Biye Ren
ABSTRACT In order to apply reversible self- and dis-assembly processes of polymers controlled by electrochemical redox to drug delivery systems, two novel polymeric ferrocenyl amphiphiles, 4-(11-Ferrocenylundecyloxy) benzoic acid methoxy poly(ethylene glycol) ester (denoted as PEG-Ph-Fc) and (11-ferroceny -lundecyloxy) poly(ethylene glycol) methyl ether (denoted as PEG-Fc) were synthesized and their electrochemical redox-controlled self-assembly behaviors in aqueous solution were investigated by potentiostatic method and observed by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). It is observed that polymeric amphiphile PEG-Fc and PEG-Ph-Fc could reversibly aggregate to form spherical micelles and also disassemble into irregular fragments by electrochemical redox reaction in aqueous solution without adding other chemical reagents. This work offers significant possibilities for the fundamental science of controlled self-assembly and drug release.
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危险品化学品经营许可证（带存储）