MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Yupeng Liu,Fangying Yu,Suhuan Dai,Tingting Meng,Yun Zhu,Guoxi Qiu,Lijuan Wen,Xueqing Zhou,Hong Yuan,Fuqiang Hu
Stemness and metastasis are the two main challenges in cancer therapy and are related to disease relapse post-treatment. They both have a strong correlation with chemoresistance and poor prognosis, ultimately leading to treatment failure. It has been reported that chemotherapy can induce stemness and metastasis in many cancer types, especially treatment with the chemotherapeutic agent doxorubicin (DOX) in breast cancer. A combination treatment is an efficient and elegant approach in cancer therapy through simultaneous delivery of two or more drugs with a delivery system for its synergistic effect, which is not an additive of two individual drugs. Herein, we report a combinatorial system with DOX and all-trans retinoic acid (ATRA) to address both of the above issues. As a common critical regulatory factor for oncogenic signal transduction pathways, Pin1 is a specific isomerase highly expressed within various tumor cells. ATRA, a newly identified Pin1 inhibitor, can abolish several oncogenic pathways by effectively inhibiting and degrading overexpressed Pin1. We successfully developed a folic acid (FA)-modified chitosan (CSO)-derived polymer (FA-CSOSA) and obtained FA-CSOSA/DOX and FA-CSOSA/ATRA drug-loaded micelles. FA modification can improve the uptake of the nanoparticles in tumor cells and tumor sites via folate receptor-mediated cell internalization. Compared to treatment with DOX alone, the combined treatment induced 4T1 cell apoptosis in a synergistic manner. Reduced stemness-related protein expression and inhibited metastasis were observed during treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA and were found to be associated with Pin1. Further in vivo experiments showed that treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA resulted in 85.5% tumor inhibition, which was 2.5-fold greater than that of cells treated with DOX·HCl alone. This work presents a new paradigm for addressing chemotherapy-induced side effects via degradation of Pin1 induced by tumor-targeted delivery of DOX and ATRA.
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高影响因子
CELLULOSE
·
2020
·Vol. 27
·期 15
·9123-9134
·
IF 4.21
Zhou Jianhua,Wang Lin,Zha Xianghua,Li Xiang
Abstract Ag/fluorine-containing polyacrylate latex was successfully synthesized via Pickering emulsion polymerization using Ag/poly(2-dimethylaminoethyl methacrylate- co -hexafluorobutyl acrylate) (Ag/P(DMAEMA- co -HFBA)) hybrid micelles as particle emulsifiers. The influences of introducing the Ag nanoparticles (NPs) component and the concentration of Ag/P(DMAEMA- co -HFBA) hybrid micelles on emulsion polymerization and finished cotton fabric properties were studied. The results showed that the Ag/fluorine-containing polyacrylate latex had a higher conversion, smaller particle size than the fluorine-containing polyacrylate latex using P(DMAEMA- co -HFBA) micelles as emulsifiers, indicating the positive effect of Ag NPs on emulsion polymerization. And thermogravimetric analysis (TGA) proved that Ag NPs improved the thermal stability of the latex film. Moreover, the surface of the cotton fabric finished by Ag/fluorine-containing polyacrylate latex showed more rough morphology, better hydrophobicity and excellent antibacterial activity owing to the synergistic effect of the cationic fluorine-containing polyacrylate compounds and Ag nanoparticles. Meanwhile, the presence of Ag NPs also improved the tensile strength of the finished cotton fabric, but reduced slightly the whiteness. When the concentration of Ag/P(DMAEMA- co -HFBA) hybrid micelle emulsifier was 8 mg/mL, the Ag/fluorine-containing polyacrylate latex particles presented regular raspberry-shaped with an average diameter of 120 nm, and the water/oil contact angles of finished cotton fabric attained 145° and 90°, respectively. In addition, the finished cotton fabric exhibited excellent antibacterial properties against both S. aureus and E. coli as the concentration of Ag/P(DMAEMA- co -HFBA) hybrid micelles was 12 mg/mL. The mechanism for the formation of Ag/fluorine-containing polyacrylate latex was proposed. Graphic abstract
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PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2020
·Vol. 37
·期 4
·2000044
·
IF 3.099
Kehan Xu,Na Xu,Yanchao Zhu,Mengsi Zhang,Weijun Tang,Yun Ding,Aiguo Hu
Conformity of two biological imaging entities, magnetic resonance imaging (MRI) and fluorescence imaging, is achieved through co-assembly of a Gd(III)-based metallosurfactant, conjugated polymeric nanoparticles, and amphiphilic block copolymer F127 (PEO 106 PPO 70 PEO 106 ) followed by crosslinking with organosilica. The cross-linked micelles with a size around 100 nm exhibit outstanding dispersion stability in aqueous and phosphate buffered saline solutions, bright fluorescence emission, and high relaxivities, providing a new approach to synthesize highly efficient bimodal contrast agents. The relaxivities of the co-assembled micelles are synergistically enhanced by incorporation of Gd(III) complexes with high hydration number ( q = 3) and elongation of rotation correlation time to achieve r 1 values up to 105.37 m m −1 s −1 (at 1.5 T), which is over 20 times that of clinically used MRI contrast agents and among the highest values of all the nanoparticular MRI contrast agents. The external PEO layer endows these micelles with very low cytotoxicity for both in vitro and in vivo imaging. Meanwhile, thanks to the enhanced permeability and retention effect originating from their nanoscale sizes, the bimodal contrast agents show a prolonged blood circulation time in vivo and targeted accumulation at tumor regions to display outstanding MRI imaging performance.
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Pharmaceutics
·
2019
·Vol. 11
·期 3
·107
·
IF 4.773
Huiyun Zhang,Qilong Wang,Congyong Sun,Yuan Zhu,Qiuxuan Yang,Qiuyu Wei,Jiaxin Chen,Wenwen Deng,Michael Adu-Frimpong,Jiangnan Yu,Ximing Xu
6-shogaol is a promising anti-cancer and anti-inflammatory agent. However, the treatment effectiveness of 6-shogaol is limited by poor water solubility, poor oral absorption and rapid metabolism. Herein, 6-shogaol loaded in micelles (SMs) were designed to improve 6-shogaol’s solubility and bioavailability. The micelles of a PEG derivative of linoleic acid (mPEG2k-LA) were prepared by the nanoprecipitation method with a particle size of 76.8 nm, and entrapment of 81.6 %. Intriguingly, SMs showed a slower release in phosphate buffer saline (PBS) (pH = 7.4) compared to free 6-shogaol while its oral bioavailability increased by 3.2–fold in vivo. More importantly, the in vitro cytotoxic effect in HepG2 cells of SMs was significantly higher than free 6-shogaol. Furthermore, SMs could significantly improve the tissue distribution of 6-shogaol, especially liver and brain. Finally, SMs showed a better hepatoprotective effect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo than free 6-shogaol. These results suggest that the novel micelles could potentiate the activities of 6-shogaol in cancer treatment and hepatoprotection.Keywords:6-shogaol;cytotoxic effect;HepG2 cells;micelles;hepatoprotection
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高影响因子
DYES AND PIGMENTS
·
2019
·
IF 4.018
Siyao Zhu,Feifei Zhao,Mingxiao Deng,Tianyi Zhang,Changli Lü
The nanostructured hybrid assembly has gained growing interest due to their unique electronic, optical and catalytic properties . Herein, a novel ratiometric fluorescent sensor was constructed by coupling blue-green emission carbon dots (CDs) to a block copolymer micelle-encapsulated red-emission CdSe/ZnS QDs through host-guest interaction. The carbon dots (CDs) were prepared by carbonization of β-cyclodextrin (β-CD) via a simple hydrothermal process. The amphiphilic diblock copolymer AZO-PNIPAM-b-P(St-co-MQ) containing azobenzene (AZO)-terminated hydrophilic poly( N -isopropylacrylamide) (PNIPAM) block and hydrophobic polystyrene (PS) block was synthesized by a typical RAFT polymerization . The 5-(2-methacryloylethyloxymethyl)-8- quinolinol (MQ) units were introduced into PS block, which could make CdSe/ZnS QDs to be embedded into the core of the block polymer micelles via coordination interaction in the self-assembling process. The as-fabricated β-cyclodextrin derived CDs-coupled block copolymer hybrid micelles loaded with CdSe/ZnS QDs as a fluorescence sensor exhibited dual emission peaks of CDs centered at 450 nm and CdSe/ZnS QDs at 620 nm with a large peak separation of 170 nm upon excitation at 360 nm. And the as-prepared hybrid micelles as a ratiometric fluorescence sensor can be applied to detect Hg 2+ and Cu 2+ with the detection limits down to 1.6 and 2.74 μM, respectively.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Haitao Huang,Xiaolan Zhang,Jiahui Yu,Junping Zeng,Peter R. Chang,Haibo Xu,Jin Huang
This work is aimed at the development of a reduction-sensitive drug carrier for the delivery of the anti-cancer drug paclitaxel (PTX). N,N′-bis(acryloyl)cystamine (CBA) was reacted with ethanolamine (AEOL) via Michael addition to synthesize cationic poly(CBA-AEOL) (PCA) containing disulfide bonds. Subsequently, polycaprolactone (PCL) was grafted from PCA to form a novel reduction-sensitive copolymer (PCA-g-PCL). The PCA-g-PCL copolymer self-assembled as spherical micelles with a mean size of ca. 108 nm. The disulfide bonds in the PCA-g-PCL copolymer contributed to the reduction-sensitivity of the micelles, observed as stepwise aggregation under simulated reduction conditions. To improve the stability of PCA-g-PCL micelles in aqueous media, carboxyl-terminated poly(ethylene glycol) methyl ether (mPEG-COOH) was conjugated with the PCA-g-PCL copolymer via electrostatic interaction to produce polyion complex micelles with a hydrophilic PEG surface. The in vitro release of PTX from the mPEG@PCA-g-PCL micelle showed a reduction sensitive profile, namely the rate of drug release strongly depended upon the concentration of the reducing agent. Leakage of PTX was limited to below 30% under normal conditions while almost all the drug was released in 9 h under reduction conditions with 40 mM DTT. In conclusion, the assembled mPEG@PCA-g-PCL micelle with reduction-sensitive controlled release shows great potential for improving the therapeutic effect of paclitaxel.
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高影响因子
POLYMER
·
2010
·
IF 3.573
Jianbo Li,Jie Ren,Yang Cao,Weizhong Yuan
Biodegradable star-shaped poly( ɛ -caprolactone) and poly( ɛ -caprolactone- b - l -lactide) (5sPCL- b -PLLA) with five arms were synthesized by ring-opening polymerization (ROP) from an asymmetric BIS-TRIS core via “core-first” strategy. Subsequently, a series of amphiphilic and double responsive star-block copolymers were synthesized by Z -RAFT star polymerization of N , N -dimethylamino-2-ethyl methacrylate (DMAEMA) from the star-shaped macro-RAFT agent, which was prepared by attaching 3-benzylsulfanylthiocarbonylthiocarbonylsufanylpropionic acid (BSPA) to 5sPCL- b -PLLA using a simple two-step reaction sequence. GPC and 1 H NMR data demonstrated the polymerization courses are under control. The molecular weight of 5sPCL- b -PLLA- b -DMAEMA increased with the monomer conversion, and the molecular weight distribution was in the range of 1.19–1.37. The spherical micelles with degradable core and pH/thermo-double sensitive shell had been prepared from the aqueous medium of the amphiphilic star-shaped copolymers by dialysis method. Both pH and thermal-responsive behaviours of copolymer micelles obtained in this study were investigated. The micelle size and morphology were measured by DLS, AFM and TEM .
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高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Dishi Wang,Yanxia Zhou,Xinru Li,Xiaoyou Qu,Yunqiang Deng,Ziqi Wang,Chuyu He,Yang Zou,Yiguang Jin,Yan Liu
pH-responsive polymeric micelles have shown promise for the targeted and intracellular delivery of antitumor agents. The present study aimed to elucidate the possible mechanisms of pH-sensitivity and cellular internalization of PEOz-b-PLA micelles in detail, further unravel the effect of hydrophilic/hydrophobic ratio of the micelles on their cellular internalization, and examine the intracellular trafficking routes and fate of PEOz-b-PLA after internalization of the micelles. The results of variations in the size and Zeta potential of PEOz-b-PLA micelles and cross-sectional area of PEOz-b-PLA molecules with pH values suggested that electrostatic repulsion between PEOz chains resulting from ionization of the tertiary amide groups along PEOz chain at pH lower than its pKa was responsible for pH-sensitivity of PEOz-b-PLA micelles. Furthermore, the studies on internalization of PEOz-b-PLA micelles by MCF-7 cells revealed that the uptake of PEOz-b-PLA micelles was strongly influenced by their structural features, and showed that PEOz-b-PLA micelles with hydrophilic/hydrophobic ratio of 1.7–2.0 exhibited optimal cellular uptake. No evident alteration in cellular uptake of PEOz-b-PLA micelles was detected by flow cytometry upon the existence of EIPA and chlorpromazine. However, the intracellular uptake of the micelles in the presence of MβCD and genistein was effectively inhibited. Hence, the internalization of such micelles by MCF-7 cells appeared to proceed mainly through caveolae/lipid raft-mediated endocytosis without being influenced by their hydrophilic/hydrophobic ratio. Confocal micrographs revealed that late endosomes, mitochondria and endoplasmic reticulum were all involved in the intracellular trafficking of PEOz-b-PLA copolymers following their internalization via endocytosis, and then part of them was excreted from tumor cells to extracellular medium. These findings provided valuable information for developing desired PEOz-b-PLA micelles to improve their therapeutic efficacy and reducing the potential safety risks associated with their intracellular accumulation.
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高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Gaojin Zhou,Zhaojin Zhang,Subhan Mahmood,Jie Tang,Shun Yao
For the first time, two kinds of green solvents including ionic liquid (IL) and deep eutectic solvent (DES) were combined for achieving flavonoids and terpenoids simultaneously from Ginkgo leaves. They were applied in the form of micelles and the complex with natural carbon dots (CDs) as extraction and separation mediums, respectively. Especially, the latter was prepared from the lignocellulosic residue of Ginkgo leaves after extraction, which achieved the comprehensive utilization of natural resources. Critical micelle concentrations (CMC) of the IL were determined as 4.70–5.38 in the range from 5 to 45 °C, and the main particle size of CDs was found between 20 and 25 nm. After comprehensive characterization on them, a biphasic system composed of IL micelles and CDs@DES was constructed, with the former in the upper layer and the latter in the lower layer. Then it was successfully applied for obtaining flavonoids and terpenoids from the leaves of Ginkgo biloba with extraction efficiency of 96.2 % and 93.2 % respectively, which were analyzed by liquid chromatography-mass spectrum (LC-MS). Moreover, the IL and DES could be repeatedly used through the post-treatment.
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高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2026
·Vol. 28
·期 9
·221
·
IF 3.5
Li Rongye,Zhu Congying,Song Xiaoping,Zhang Xiaodong,Hamdi Marwa,Chen Jiahong
Recent advances in polymeric nanocarriers have highlighted the potential of amphiphilic block copolymers for the simultaneous delivery of chemotherapeutic agents with different physicochemical properties. In this study, asymmetric poly(ethylene glycol)-b-polylactide-b-poly(ethylene glycol) (PEG- b -PLA- b -PEG) triblock copolymers were synthesized via ring-opening polymerization, end-group functionalization, and click coupling, and subsequently evaluated as biodegradable nanocarriers for the co-delivery of paclitaxel (PTX) and cisplatin (CDDP). The copolymers were characterized by 1 H nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Self-assembly in aqueous media yielded spherical micelles with uniform size distributions, as confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The micelles exhibited efficient encapsulation of PTX and CDDP with high drug-loading capacities and encapsulation efficiencies. Hydrolytic degradation studies conducted at 37 °C for 45 days revealed progressive cleavage of the ester bond, reduction in molecular weight, and gradual disintegration of the micellar structure. In vitro release studies of single- and dual-drug-loaded micelles demonstrated sustained release of both drugs over time. Analysis of the release data using the Korsmeyer–Peppas model provided insight into the release behavior and suggested contributions from both diffusion and polymer degradation processes. The biocompatibility of the unloaded triblock copolymer micelles was assessed through cytocompatibility, hemocompatibility, and zebrafish embryo assays, which indicated low intrinsic toxicity and minimal hemolytic activity. Collectively, these results demonstrate that PEG- b -PLA- b -PEG triblock copolymer micelles can be recognized as biodegradable carriers capable of dual-drug encapsulation and sustained release, providing a useful platform for further investigation of combination drug delivery systems. Graphical abstract Asymmetric PEG- b -PLA- b -PEG triblock copolymers were synthesized and self-assembled into uniform micelles capable of co-encapsulating Paclitaxel and Cisplatin. The micellar architecture provided controlled degradation and synchronized dual-drug release over 45 days. The combination of tunable structure, sustained release, and excellent biocompatibility highlights these triblock copolymer micelles as efficient nanocarriers for combinational cancer therapy
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International Journal of Nanomedicine
·
2023
·
IF 8
Hao Wu,Qingxiang Zhong,Rongling Zhong,Houcai Huang,Zhi Xia,Zhongcheng Ke,Zhenhai Zhang,Jie Song,Xiaobin Jia
Oleanolic acid (OA) is a triterpenoid found in various fruits and vegetables and used in traditional Chinese medicine. OA plays a crucial role in the treatment of several cancers, but poor water solubility, low permeability, and significant efflux have limited its widespread clinical use. Vitamin E-d-α-tocopheryl polyethylene glycol succinate (vitamin E-TPGS) and Pluronic P105 were used to improve the solubility and permeability and to decrease the efflux of OA. OA-loaded mixed micelles were prepared by ethanol thin-film hydration. The physicochemical properties of the micelles, including zeta potential, morphology, particle size, solubility, drug loading, and drug entrapment efficiency were characterized. OA release from micelles was slower than that from the free drug system. OA uptake by A549 non-small-cell lung cancer (NSCLC) cells was enhanced by the micelles. A tumor model was established by injecting A549 cells into nude mice. In vivo imaging showed that OA-micelles could accumulate in the tumors of nude mice. Additionally, smaller tumor size and increased expression of pro-apoptotic proteins were observed in OA-micelle-treated mice, indicating that OA-micelles are more effective than free OA in treating cancer. In vitro experiments were performed using two NSCLC cell lines (A549 and PC-9). Cytotoxicity evaluations showed that the half-maximal inhibitory concentrations of free OA and OA-micelles were 36.8±4.8 and 20.9±3.7 μM, respectively, in A549 cells and 82.7±7.8 and 56.7±4.7 μM, respectively, in PC-9 cells. Apoptosis assays revealed that the apoptotic rate of OA-micelle-treated A549 and PC-9 cells was higher than that of cells treated with the same concentration of free OA. Wound healing and transwell assays showed that migration and invasion were significantly suppressed in OA-micelle-treated cells. Immunofluorescence and Western blot analyses confirmed that the epithelial–mesenchymal transition was reversed in OA-micelle-treated cells. Mixed micelles are a promising nano-drug delivery system for lung cancer treatment.
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高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2022
·Vol. 34
·期 4
·1209-1219
·
IF 3.348
Wenju Hu,Haozhi Sun,Lixia Pan,Chaoqun Zhang,Xin Shen,Feng Su,Jie Song
The encapsulation and release of hydrophobic drugs from polymersomes are of great importance in drug delivery. A significant challenge is to enhance the encapsulation capacity of finding better drug-polymer compatibility. Herrin, poly(trimethylene carbonate)-b-poly(ethylene glycol) (PTMC-PEG) diblock copolymers were successfully synthesized by ring opening polymerization of trimethylene carbonate using monomethoxy poly(ethylene glycol) (mPEG) as macro-initiator and stannous octoate as catalyst. The resulting diblock copolymer were characterized by 1 H NMR, FTIR, GPC, and DSC techniques. Blank and paclitaxel (PTX) loaded micelles was prepared by co-solvent evaporation method and characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). The influence of hydrophilic/hydrophobic segment length to drug loading and release was explored. All micelles have the sustained hydrophobic drug release properties of the micelles. Moreover, the cytotoxicity of micelles was evaluated by MTT and live-dead cell staining assay using L929 cell lines, showing the good biocompatibility. Therefore, PTMC-PEG micelles could be a suitable material for the loading and releasing of hydrophobic drugs.
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