查找使用阿拉丁产品的科研文献

Co-delivery of docetaxel and retinoic acid by poly (ethylene glycol)-retinoic acid conjugates based micelles for synergistic prostate cancer therapy

Hang Hu,Defeng Xu

In the present work, docetaxel (DTX) and retinoic acid (RA) co-loaded micelles were developed for synergistic prostate cancer therapy. PEG-RA and RA-PEG-RA were synthesized and subsequently used for loading of DTX and RA. The as prepared DTX/RA@RA-PEG-RA micelles exhibit smaller size and higher drug loading capacity as compared to DTX/RA@PEG-RA micelles. The in vitro drug release study shows that DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles exhibit similar drug release behaviours in which DTX exhibits fast release and RA exhibits sustained release. Nile red (NR) was loaded into PEG-RA and RA-PEG-RA micelles to investigate the cellular uptake of the micelles by fluorescence microscope and flow cytometry. The results show that NR@RA-PEG-RA micelles exhibit slightly enhanced cellular uptake as compared to NR@PEG-RA micelles. The cellular uptake of DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles determined by HPLC also show similar results. In in vitro cytotoxicity against C4-2 and 22Rv1 cells, DTX in combination with RA exhibit synergistic antitumor effect, and DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles exhibit enhanced cytotoxicity against C4-2 cells and similar cytotoxicity against 22Rv1 cells as compared to DTX/RA. DTX/RA@PEG-RA and DTX/RA@RA-PEG-RA micelles show significant potential for prostate cancer therapy.

Acetal-linked polymeric prodrug micelles based on aliphatic polycarbonates for paclitaxel delivery: preparation, characterization, in vitro release and anti-proliferation effects

Shiya Zhou,Shuwen Fu,Hanle Wang,Yanhao Deng,Xing Zhou,Wei Sun,Yinglei Zhai

Acidic tumor microenvironment has been extensively explored to design pH-responsive paclitaxel prodrug micelles for cancer therapy. The object of this study is to investigate the pH-responsive drug release behavior and the anti-proliferation capacity of acetal-linked paclitaxel polymeric prodrug micelles. The prodrug was synthesized and evaluated for paclitaxel content. The prodrug micelles were fabricated and characterized for morphology, size, in vitro pH-responsive paclitaxel release, cellular uptake, and anti-proliferation. Paclitaxel content was 33 wt%. The prodrug micelles exhibited spherical structure with the hydrodynamic diameter of 154 nm. Besides, the in vitro paclitaxel release behavior was verified to be pH-responsive, and 77%, 38%, and 17% of parent free paclitaxel was released from the nano-sized prodrug micelles in 13 h at pH 5.5, 6.5, and 7.4, respectively. The cellular uptake assessment demonstrated the time-dependent internalization of prodrug micelles. Meanwhile, CCK-8 analysis showed that prodrug micelles possessed the potent anti-proliferation effects. Prodrug micelles based on aliphatic polycarbonates present a promising platform for cancer chemotherapy due to the pH-responsive characteristics of acetal bond, potent anti-proliferation effects, and outstanding cytocompatibility of aliphatic polycarbonates.

Exogenous Vitamin C-Triggered Surface Charge Conversion of pH/Reduction-Responsive Micelles for the Enhanced Tumor-Specific Activity of Loaded Doxorubicin

Zhengzhong Wu,Bin Chen,Ziying Gan,Fan Chen,Xianglin Luo

The effective accumulation at tumor sites and endocytosis by tumor cells for anticancer agents in carriers are essential in successful cancer therapy, and both of the processes are affected by the surface charge of drug carriers. In this study, vitamin C (VC) was employed as an “exogenous switch” to trigger the surface charge conversion of DOX-loaded micelles to obtain a better antitumor effect. T micelles formed by poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL–PDEA-ss-PMPC) turned their ζ potentials from +1 mV to +18 mV under treatment of 20 mM VC, while the ζ potentials of control R micelles formed by PCL-ss-P(DEA-r-MPC) almost remained unchanged under the same condition. DOX-loaded T@DOX and R@DOX had high DLCs of 12% and 13.8%, respectively, and both showed an accelerated drug release in a reductive environment (10 mM GSH or 20 mM VC) at pH 5.0. Notably, due to the surface charge conversion and fast drug release triggered by VC, T@DOX/VC (T@DOX was pretreated by VC) showed an enhanced cytotoxicity and cellular uptake superior to T@DOX, R@DOX, and R@DOX/VC. T@DOX/VC also displayed the in vivo antitumor effect well, which was comparable to DOX·HCl but with less toxic side effects than DOX·HCl. In summary, VC as an exogenous trigger can induce a better antitumor effect of drug-loaded micelles with a suitable polymer structure by charge conversion, and T@DOX/VC has shown to be as a promising approach to achieve potent treatment of tumors.

Light and temperature dual stimuli-responsive micelles from carbamate-containing spiropyran-based amphiphilic block copolymers: Fabrication, responsiveness and controlled release behaviors

Ruizhen Zhang,Yuting Min,Peipei Ji,Guiyang Zhou,Hong Yin,Dongming Qi,Hangjun Deng,Zan Hua,Tao Chen

With the increasing demand for treating cancer and cardiovascular diseases in recent years, drug delivery therapy using intelligent nanocarriers has been investigated intensely. Usually, hydrophobic dyes were used as drug models for the development of drug-release carriers. In this study, light and temperature dual-responsive micelles were designed and fabricated, and the controlled release property was investigated using the hydrophobic fluorescent dye coumarin 102 as the model. A carbamate-containing spiropyran methacrylate monomer (SPMA) was adopted as the photosensitive unit because it is more conducive to stabilize the micelle structure compared to traditional spiropyran. Firstly, a light and temperature dual-responsive copolymer P[DMA 50 - b -(SPMA 20 - co -NIPAAm 17 )] was synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization. Then, the copolymer was self-assembled into micelles with coumarin 102 encapsulated in the hydrophobic core above the lower critical solution temperature (LCST) and under visible light (Vis) irradiation. When the visible light was switched to ultraviolet (UV) radiation, the micelles' permeability increased as a result of the change from closed, three-dimensional spiropyrans (SP) to open, planar merocyanines (MC), resulting in the release rate of 51% for coumarin 102 in 15 min with “low” release capability. Lowering the temperature to room temperature (RT), the hydrophobic nuclei were partially destructed as a result of the changing of PNIPAAm segment from hydrophobicity to hydrophilicity. Meanwhile, the release rate was observed to be 77% in 15 min showing “medium” release capability. The micelles were almost wholly disintegrated under the dual stimulation of both UV irradiation and RT, achieving the release rate of 96% within the same time exhibiting “high ” release capability. This study offered an approach for the construction of controllable drug release carriers.

Chitosan-based nano-micelles for potential anti-tumor immunotherapy: Synergistic effect of cGAS-STING signaling pathway activation and tumor antigen absorption

Shufen Zhang,Yingping Zeng,Kai Wang,Guangtao Song,Yiru Yu,Tingting Meng,Hong Yuan,Fuqiang Hu

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway is an essential DNA-sensing pathway to regulate the innate and adaptive immune response, which plays an important role in tumor immunotherapy. Although the STING agonists can be used, they are limited by their inability to target immune cells and systemic immunotoxicity, calling for novel strategies to accurately and effectively activate the cGAS-STING signaling pathway. Herein, mannose-modified stearic acid-grafted chitosan (M-CS-SA) micelles with the ability to activate the cGAS-STING signaling pathway and absorb tumor antigens were constructed. The chitosan-based nano-micelles showed valid dendritic cell (DCs) targeting and could escape from lysosomes leading to the activation of the cGAS-STING signaling pathway and the maturation of DCs. In addition, a combinatorial therapy was presented based on the programmed administration of oxaliplatin and M-CS-SA. M-CS-SA adsorbed tumor antigens released by chemotherapy to construct an autologous tumor vaccine and built a comprehensive antitumor immune response. In vivo , the combinatorial therapy achieved a tumor inhibition rate of 76.31 % at the oxaliplatin dose of 5 mg/kg and M-CS-SA dose of 15 mg/kg, and increased the CD3 + CD8 + T cell infiltration. This work demonstrated that M-CS-SA and its co-treatment with oxaliplatin showed great potential in tumor immunotherapy.

GE11-modified carboxymethyl chitosan micelles to deliver DOX·PD-L1 siRNA complex for combination of ICD and immune escape inhibition against tumor

Panpan Song,Bingjie Wang,Qi Pan,Tianze Jiang,Xiangyan Chen,Miao Zhang,Jiaojiao Tao,Xia Zhao

Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4 + and CD8 + T cells, reduce Tregs (TGF-β), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.

Novel dual CAFs and tumour cell targeting pH and ROS dual sensitive micelles for targeting delivery of paclitaxel to liver cancer

Chunjing Guo,Wei Zhang,Qiaoyun Zhang,Yanguo Su,Xiaoya Hou,Qiang Chen,Huimin Guo,Ming Kong,Daquan Chen

Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer

Shuhang Wang,Jingxin Gou,Yue Wang,Xinyi Tan,Linxuan Zhao,Xiangqun Jin,Xing Tang

Purpose Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality and poor prognosis. In this study, we designed a liposome encapsulating polymeric micelles (PMs) loaded with vinorelbine (NVB) and cis-diamminedichloroplatinum (II) (cisplatin or CDDP) for the treatment of NSCLC.Materials and Methods Sodium poly(α-l-glutamic acid)-graft-methoxy-polyethylene glycol (PLG-G-PEG5K) was used to prepare NVB-loaded NVB-PMs and CDDP-loaded CDDP-PMs that were co-encapsulated into liposomes by a reverse evaporation method, yielding NVB and CDDP co-delivery liposomes (CoNP-lips) composed of egg phosphatidyl lipid-80/cholesterol/DPPG/DSPE-mPEG2000 at a molar ratio of 52:32:14:2. The CoNP-lips were characterized in terms of particle size, zeta potential, drug content, encapsulation efficiency, and structural properties. Drug release by the CoNP-lips as well as their stability and cytotoxicity was evaluated in vitro, and their antitumor efficacy was assessed in a mouse xenograft model of Lewis lung carcinoma cell-derived tumors.Results CoNP-lips had a spherical shape with uniform size distribution; the average particle size was 162.97±9.06 nm, and the average zeta potential was −13.02±0.22 mV. In vitro cytotoxicity analysis and the combination index demonstrated that the CoNP-lips achieved a synergistic cytotoxic effect at an NVB:CDDP weight ratio of 2:1 in an NSCLC cell line. There was sustained release of both drugs from CoNP-lips. The pharmacokinetic analysis showed that CoNP-lips had a higher plasma half-life than NP solution, with 6.52- and 8.03-fold larger areas under the receiver operating characteristic curves of NVB and CDDP. CoNP-lips showed antitumor efficacy in tumor-bearing C57BL/6 mice and drug accumulation in tumors via the enhanced permeability and retention effect.Conclusion CoNP-lips are a promising formulation for targeted therapy in NSCLC.

Enhancement of oral bioavailability and anti-colitis effect of luteolin-loaded polymer micelles with RA (rosmarinic acid)-SS-mPEG as carrier

Zhaomin Lu,Juan Liu,Liangjian Zhao,Chenli Wang,Feng Shi,Zhengqi Li,Xuesong Liu,Zhiwei Miao

Objective Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNBS)-induced ulcerative colitis (UC) model in rats.Methods The synthetic RA-SS-mPEG was characterized with NMR spectroscopy, before preparation of luteolin-coated RA-SS-mPEG polymer micelles. The in vitro characterization and evaluation of the formulation were accomplished, couple with its pharmacokinetic parameters. The levels of PEG2, MDA, CRP and GSH, as well as concentrations of TNF-α, IL1-β, IL-6 and IL-10 in serum and colon tissue were detected via ELISA kit. The degree of colon injury and inflammation was evaluated via histopathologic examination.Results L-RSPMs displayed small average droplet size (133.40 ± 4.52 nm), uniformly dispersed (PDI: 0.163 ± 0.011), good stability, slow release and enhanced solubility. We observed 353.28% increase in the relative bioavailability of L-RSPMs compared to free luteolin, while the half-life of the micelle was extended by 6.16h. Compared to model (M) group, luteolin (low and high doses) and L-RSPMs (low and high doses) significantly reduced levels of MDA, PEG2, CRP, TNF-α, IL-6 and IL-1β in colon tissue and serum of colitic rats but dose dependently increased IL-10 and SOD levels (p < 0.01). Histopathologic examination of colon showed that luteolin (low and high doses) and L-RSPMs (low and high doses) improved colonic inflammation in colitic rats to varying degrees compared to M group.Conclusion L-RSPMs could improve TNBS-induced colon inflammation by enhancing bioavailability, promoting antioxidant effects and regulating cytokine release, which may become a potential agent for UC treatment in clinical settings.

Polypeptides Micelles Composed of Methoxy-Poly(Ethylene Glycol)-Poly(l-Glutamic Acid)-Poly(l-Phenylalanine) Triblock Polymer for Sustained Drug Delivery

Xingzheng Liu,Rongrong Fan,Boting Lu,Yuan Le

Methoxy-poly(ethylene glycol)-poly(l-glutamic acid)-poly(l-phenylalanine) triblock polymers with different architecture were synthesized as drug carrier to obtain sustained and controlled release by tuning the composition. These triblock polymers were prepared by ring opening polymerization and poly(ethylene glycol) was used as an initiator. Polymerization was confirmed by1H NMR, FT-IR and gel penetration chromatography. The polymers can self-assemble to form micelles in aqueous medium and their critical micelle concentrations values were examined. The micelles were spherical shape with size of 50–100 nm and especially can arranged in a regular manner. Sorafenib was selected as the model drug and the drug loading performance was dependent on the composition of the block copolymer. In vitro drug release indicated that the polymers can realize controlled and sustained drug release. Furthermore, in vitro cytotoxicity assay showed that the polymers were biocompatible and the drug-loaded micelles can increase toxicity towards tumor cells. Confocal fluorescence microscopy assays illustrated that the micelles can be uptaken quickly and release drug persistently to inhibit tumor cell growth.Keywords:methoxy-poly(ethylene glycol);polypeptide;methoxy-poly(ethylene glycol)-poly(l-glutamic acid)-poly(l-phenylalanine);micelles;drug delivery

Redox-sensitive micelles based on retinoic acid modified chitosan conjugate for intracellular drug delivery and smart drug release in cancer therapy

Tingting Luo,Jingtian Han,Feng Zhao,Xiaohong Pan,Baocheng Tian,Xiujuan Ding,Jing Zhang

Novel chitosan-cystamine-retinoic acid conjugate (CS-SS-RA) was synthesized and could self-assemble into redox-sensitive micelles in aqueous environment with low critical micelle concentration value. CS-SS-RA micelles were characterized with spherical shape, desirable particle size, negative zeta potential, high paclitaxel (PTX) loading and encapsulation efficiency and redox-sensitivity. Hemolysis and cytotoxicity studies proved the safety of CS-SS-RA micelles for intravenous administration. Cytotoxicity study against HepG2 cells and the growth inhibition study on three-dimensional multicellular tumor spheroids (MCTSs) revealed that PTX-loaded CS-SS-RA micelles exhibited higher antitumor activity than free PTX. The in vitro cellular uptake profiles of FITC-labeled CS-SS-RA micelles evaluated via confocal laser scanning microscopy and flow cytometry indicated that CS-SS-RA micelles could enhance cellular uptake efficiency of PTX, and their internalization by HepG2 cells were mediated by clathrin-mediated endocytosis and macropinocytosis. These results demonstrated that CS-SS-RA micelles could be developed as a promising platform for intracellular delivery of hydrophobic antitumor agents.

Preparation of quadruple responsive polymeric micelles combining temperature-, pH-, redox-, and UV-responsive behaviors and its application in controlled release system

Yeqing Dong,Xiaoyan Ma,Haohui Huo,Qilu Zhang,Fengjin Qu,Fang Chen

A novel series of quadruple responsive copolymers, poly(ethylene glycol)- ss -[poly(dimethylaminoethyl methacrylate)- co -poly(2-nitrobenzyl methacrylate)] [PEG- ss -(PDMAEMA- co -PNBM)], were synthesized via atom transfer radical polymerization mediated by home-made PEG-based macro-initiator labeled with disulfides. The obtained copolymers could self-assemble in aqueous solution forming micelles with the disulfide bridge linking the hydrophilic coronas (PEG) and the hydrophobic cores (PDMAEMA- co -PNBM). Investigation on the resulted micelles indicated that the micelles could respond to various stimuli, that is, temperature, pH, the presence of dithiothreitol (DTT), and UV irradiation. Moreover, the responsive behavior of the micelles depends on the type of stimuli, that is, temperature change causes size change of the micelles, while UV irradiation leads to dissolution of the self-assembled structures. Such stimulus-dependent responsive behavior could be applied in smart materials that deal with multi-tasks or in the construction of complex logic gate. The potential application of the multi-responsive micelles in cargo release system was also evaluated using Nile Red (NR) as model molecule. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 46675.