ANTICANCER RESEARCH
·
2018
·Vol. 38
·期 1
·219-225
·
IF 1.865
CAIYUN DENG,CHANG XU,XIAOMIN ZHANG,JU YAO,YINGXIN ZHANG,BO YU,ROBERT J. LEE,CHENGJUN JIANG
Background/Aim: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable. Materials and Methods: Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide)-9-fluorenylmethoxycarbonyl-L-phenylalanine (mPEG-PDLLA-Phe(Fmoc)) was synthesized through a classical esterification reaction. Paclitaxel-loaded mPEG-PDLLA-Phe(Fmoc) micelles (PTX-PheMs) were prepared by the self-assembly method. Composition, structure and physicochemical properties were characterized. Pharmacokinetics were evaluated in rats. Therapeutic effect was evaluated in tumor-bearing mice. Safety profile was assessed by a hemolysis assay and an acute-toxicity study. Results: The average size of PTX-PheMs was about 45 nm. The hemolysis and acute-toxicity tests confirmed its biocompatibility and safety. The pharmacokinetics and therapeutic effect experiments demonstrated its long circulation property and superior antitumor effect. Conclusion: mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Xiumei Zhu,Altansukh Tsend-Ayush,Zhongyue Yuan,Jing Wen,Jiaxin Cai,Shifu Luo,Jianxu Yao,Junxing Bian,Linfang Yin,Jianping Zhou,Jing Yao
In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6 ± 1.2 nm with a low poly-dispersity index (0.224 ± 0.013) and negative zeta potential (−16.30 mV). The drug loading and entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations and in vivo imaging studies revealed that TGA PMs displayed higher cellular uptake and selective accumulation at the tumor site, indicating good tumor targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the control group. This could be due to TGA-mediated targeted drug delivery to the hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have the potential to be used as a targeted drug delivery system for hepatic cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2019
·
IF 2.442
Yan Zheng,Shudan Shi,Yaru Liu,Yandan Zhao,Yuqi Sun
Liver cancer is one of the most common malignant tumors. Chemotherapy drugs have been widely used in the anti-hepatoma research. However, low targeting efficiency and serious adverse reaction are their main drawbacks. Liver tumor was proved to have a slightly acidic microenvironment (pH 4.5–5.5) and many glycyrrhetinic-acid-specific binding sites. Therefore, in the present study, the glycyrrhetinic acid- and hydrazone bond-modified micelles were designed. mPEG-HZ-PLA and GA-PEG-PLA copolymer were synthesized to prepare glycyrrhetinic-acid-modified pH-sensitive polymeric micelles (GA-PEG-HZ-PLA). The targeted pharmacokinetics was used to evaluate the effect in hepatoma 22 tumor-bearing mice after the micelles were administered intravenously. The contents of coumarin-6 in blood and tissues were determined through high-performance liquid chromatography using a fluorescence detection (HPLC-FLD) with coumarin-30 as inner standard. The micelles have shown long-circulation effects and two-department models. In the targeting pharmacokinetics, the relative intake efficiency, targeted efficiency, relative targeting efficiency, and concentration ratio of GA-PEG-HZ-PLA in the tumor were 3.24, 4.04, 3.00, and 2.47, respectively. We have demonstrated that GA-PEG-HZ-PLA was more effectively accumulated in the liver and tumor. Thus, the prepared active-targeted and pH-sensitive micelles modified with glycyrrhetinic acid structure and hydrazone bond are promising tools for effective liver cancer therapy.
研究领域:
药学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2017
·
IF 1.194
Wei Wang,Biyun Zhao,Xiangyang Meng,Pan She,Pantian Zhang,Yi Cao,Xuefei Zhang
The traditional chemotherapy using single agent may suffer from serious drawbacks, particularly dose-limiting toxicity and relatively low antitumor efficacy, which can lead to failure of chemotherapy. Co-delivery of two or more therapeutic drugs in nanotechnology is a potential strategy to generate synergistic anticancer effects and reduce individual drug-related toxicity, but explosive release of each drug from multi-drug loaded nanoparticles has been a distinct obstacle. In this study, a novel amphiphilic and biodegradable triblock copolymer , named MPEG-b-norbornene functional PLA-b-P(α-BrCL), was constructed to covalently conjugate dual anticancer drugs , i.e., doxorubicin (DOX) and paclitaxel (PTX). The resultant P-PTX-DOX prodrugs were confirmed by 1 H NMR and HPLC. By adjusting the length of PLA and PCL, it was shown that this polymer could carry relatively sufficient amount of both drugs (12.1 wt% of PTX and 15.8 wt% of DOX, respectively). Moreover, the drug release profile of P-PTX-DOX in vitro was also analyzed, which showed the desired drug release in a sustained manner. Cytotoxicity study indicated synergistic effects of P-PTX-DOX self-assembled micelles in suppression of proliferation of A549 cancer cells. In summary, a novel polyester-based copolymer was developed to covalently conjugate dual-drug, which exhibited controlled drug release behavior and synergistic anti-cancer efficacy in vitro.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Sheng Wang,Shupeng Li,Na Liang,Siyi Li,Xiaoxin Li,Pengfei Yan,Shaoping Sun
In this study, an amphiphilic polymer mPEG-HA(SA)-DNs was designed and synthesized to fabricate a multifunctional micellar system to enhance the therapeutic efficacy and reduce the toxic effect of paclitaxel (PTX). The polymer was prepared by introducing mPEG, stearic acid (SA) and 2,4-dinitrobenzenesulfonic acid (DNs) to the backbone of hyaluronic acid (HA). With above modifications, the fabricated micelles could encapsulate PTX in the core with high drug loading. The optimized PTX-loaded micelles had a mean size of 158.3 nm. Upon the effect of mPEG, the mPEG-HA(SA)-DNs micelles reduced the non-specific protein adsorption. In vitro drug release study revealed the excellent glutathione (GSH)-triggered PTX release behavior of the micelles. Moreover, GSH could trigger the detachment of DNs segment from mPEG-HA(SA)-DNs, and result in the release of SO 2 . In vitro and in vivo antitumor efficacy studies demonstrated that the PTX-loaded mPEG-HA(SA)-DNs micelles exhibited outstanding tumor suppression effect. The micelles would be potential carriers for combination cancer therapy by SO 2 and PTX.
研究领域:
药剂学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Haitao Zhang,Xiuqi Kong,Yonghe Tang,Weiying Lin
Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H2S) and their survival depends on the content of H2S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N3-Nap-PHEMA-b-PMMA-N3) micelles were prepared. Around cancer tissues, the N3-Nap-PHEMA45-b-PMMA42-N3 micelles exhibited dual characteristics of monitoring H2S and H2S triggered charge reversal with the reduction of the azido group. The surface charge of N3-Nap-PHEMA45-b-PMMA42-N3 micelles reversed from negative to positive after monitoring H2S. With H2S triggered charge reversal, the cellular uptake of DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N3-Nap-PHEMA45-b-PMMA42-N3 micelles were biocompatible to HeLa cells, and DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles showed enhanced cytotoxicity in HeLa cells in the presence of H2S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N3-Nap-PHEMA45-b-PMMA42-N3 micelles can be used as a promising platform for tumor diagnosis and therapy.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemistrySelect
·
2025
·Vol. 10
·期 15
·e202501120
·
IF 2
Peipei Ji,Xiuwu Wang,Lianpei Zhou,Guiyang Zhou,Tao Chen
Graphical This study develops polymeric micelles with Brönsted acid and pybox-Ru(II) catalysts encapsulated in hydrophobic cores for efficient one-pot tandem catalysis of deacetalization-transfer hydrogenation. The micelles, prepared via self-assembly of block copolymers, demonstrate excellent catalytic efficiency, offering a simple and effective strategy for tandem catalysis. One-pot tandem catalysis has been favored by researchers for its ability to achieve the advantage of a shortened production process. In this paper, polymeric micelles containing Brönsted acid/pybox-Ru(II) in the hydrophobic cores were prepared for one-pot tandem catalysis of deacetalization-transfer hydrogenation reaction. First, block copolymer P[NHS] 30 - b -P[PEG 2000 ] 68 containing activated ester (NHS) in the suspended chain was successfully synthesized by ring-opening metathesis polymerization (ROMP) using a functional monomer containing norbornene group (NB-NHS) and polyethylene glycol containing norbornene group (NB-PEG 2000 ) as the raw materials. Then, block copolymer P[COOH] 30 - b -P[PEG 2000 ] 68 containing Brönsted acid catalyst and complex P[pybox-Ru] 30 - b -P[PEG 2000 ] 68 containing pybox-Ru(II) catalyst were prepared by the activated ester functionalization strategy. The copolymers and complexes were characterized using nuclear magnetic resonance spectroscopy (NMR), X-ray photoelectron spectroscopy (XPS), and gel permeation chromatography (GPC). Then, polymeric micelles with the catalysts encapsulated in hydrophobic cores were achieved by the self-assembly of the above copolymers in water. The prepared polymeric micelles as catalytic nanoreactors were successfully applied to one-pot tandem catalysis of the deacetalization-transfer hydrogenation reaction, demonstrating excellent catalytic efficiency. This study provided a facile and efficient strategy for tandem catalysis.
研究领域:
化学工程
·
材料科学
·
催化化学
✓ 已验证
产品关联
DOI
高影响因子
Polymer Chemistry
·
2017
·Vol. 8
·期 46
·7160-7168
·
IF 5.375
Ting Bai,Junjie Du,Jianxin Chen,Xiao Duan,Qiang Zhuang,Heng Chen,Jie Kong
Drug delivery systems integrated with dual or multi-functionalities of stimuli-responsiveness, targeted and controlled release, and bioimaging are favorable in improving the efficiency of chemotherapy. In this study, the amphiphilic block copolymers of poly(TMC-co-DTM)-SS-POEGMA were synthesized via a combination of atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and ring opening polymerization (ROP) of two monomers (trimethylene carbonate (TMC) and N3-functional cyclic carbonate monomer (Carb-N3)) on a bifunctional initiator, followed by “click” post-functionalization with alkyne-dithiomaleimide (DTM). The obtained copolymers possessed stimuli-sensitive characteristics and bright fluorescence properties, crucial in achieving the desired therapeutic efficiency. The core-labeled micelles (CLMs) obtained from poly(TMC-co-DTM)-SS-POEGMA showed desirable fluorescence characteristics compared to the alkyne-DTM monomer. Therefore, the material was used directly in cellular uptake studies and exhibited clear green fluorescence. Moreover, the camptothecin (CPT)-loaded CLMs were shown to be stable in aqueous solution and dissociated into their hydrophobic and hydrophilic components in a thiol-rich environment to release CPT. Due to the dual functionalities of reduction-responsiveness and fluorescence, these nanoparticles based on novel poly(TMC-co-DTM)-SS-POEGMA exhibited promising characteristics to be potentially used in cancer chemotherapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Siyi Li,Kexin Li,Xianfeng Gong,Pengfei Yan,Shaoping Sun
Multifunctional polymeric micelles, which possess capabilities for tracking, bioimaging, stimuli-responsive drug release and tumor targeting, are essential in facilitating the effective delivery of anticancer drugs. Hence, a novel copolymer (CD-CS-Bio-TPAA, CCBT) was synthesized with biotin and hydroxypropyl-β-cyclodextrin conjugated chitosan as the hydrophilic segment and aggregation-induced emission (AIE) featured tetraphenylethene derivative (TPAA) as the hydrophobic segment. Interestingly, under acidic conditions, CCBT exhibited color-tunable AIE behavior as a result of the cleavage of benzoic imine bonds in TPAA molecules, transitioning from red to yellow. Furthermore, CCBT could also self-assemble into polymeric micelles and be used as drug carriers to encapsulate paclitaxel (PTX) (PTX/CCBT PMs) for self-indicating cancer therapy. In vitro release experiments demonstrated that PTX/CCBT PMs could release drugs specifically under acidic conditions. Fluorescence imaging experiments demonstrated that CCBT PMs exhibited excellent cell imaging capabilities and could be tracked due to their unique color-changing behavior. Moreover, PTX/CCBT PMs exhibited notable cytotoxic effects on MCF-7 cells and showed selective internalization by MCF-7 cells through biotin receptor-mediated active targeting. In vivo antitumor experiments confirmed that PTX/CCBT PMs possessed remarkable tumor-inhibiting effects and low systemic toxicity. This work suggested that PTX/CCBT PMs provided new ideas for self-indicating breast cancer treatment.
研究领域:
生物材料
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2016
·Vol. 17
·期 4
·1600262
·
IF 3.68
Qin Yun,Si Song Wang,Shan Xu,Jin Ping Yang,Juan Fan,Ling Lin Yang,Yue Chen,Shao Zhi Fu,Jing Bo Wu
Colorectal peritoneal carcinomatosis (CRPC) is a common systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy against CRPC is at present the preferred treatment. The aim of this study is to develop a novel hydrogel drug delivery system through the combination of 5-fluorouracil (5-FU) loaded polymeric micelles and cisplatin (DDP) in biodegradable thermosensitive chitosan (CS) hydrogel. The prepared CS hydrogel drug is a free-flowing solution at room temperature and forms a stationary gel at body temperature. Therefore, a CRPC mouse model is established to investigate the antitumor activity of CS hydrogel drug system. The results suggest that intraperitoneal administration of CS hydrogel drug can inhibit tumor growth and metastasis, and prolong survival time compared with other groups, thus improving the chemotherapeutic effect. Ki-67 immunohistochemical analysis reveals that tumors in the CS hydrogel drug group has lower cell proliferation in contrast to other groups ( P < 0.001). Furthermore, hematoxylin-eosin staining of liver and lung tissue indicates that the CS hydrogel drug has also a certain inhibitory effect on colorectal cancer metastasis to the liver and lung. Hence, the work highlights the potential clinical applications of the CS hydrogel drug.
研究领域:
肿瘤学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 84
·80896-80904
·
IF 3.289
Hongliang Cao,Huajie Song,Debiao Xie,Chao Chen,Xin Chen,Ping Wang,Wenxin Wang
We report a glutathione (GSH) responsive drug carrier that is based on the Michael addition reaction between an olefinic bond and GSH. Amphiphilic copolymers with multi-linear-cyclized and branched structures that contain vinyl groups were successfully synthesized by deactivation enhanced atom transfer radical polymerization (DE-ATRP). The polymers self-assembled into GSH responsive micelles with sizes of 68 to 97 nm and spherical morphology. The core cross-linked micelles were confirmed to greatly decrease doxorubicin (DOX) leakage due to the concentration gradient. Drug release experiments indicated that the drug carrier containing no disulfide has the same responsive ability as a conventional GSH reduction responsive carrier with a similar polymer structure. MTT assays showed that the blank micelles are totally non-cytotoxic, while the DOX-loaded micelles exhibit GSH-dependent behaviour.
研究领域:
药剂学
·
生物材料
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 98
·55139-55149
·
IF 3.708
Jinlong Yang,Chunmei Gao,Shaoyu Lü,Xinggang Wang,Mingjia Chen,Mingzhu Liu
A novel amphiphilic polymer (mPEGylated starch-deoxycholic acid, mPEG-St-DCA) was successfully prepared by grafting hydrophobic deoxycholic acid (DCA) into mPEGylated starch. According to the characterization of 1H NMR and FTIR, mPEG-St-DCA polymers could self-assemble into micelles with spherical core–shell structures. With the degree of substitution (DS) of DCA increasing, the average size of micelles (pH 7.4) decreased to below 200 nm. Correspondingly, the critical micelle concentration (CMC) decreased from 0.048 to 0.022 mg mL−1. And zeta potential values were near −2 mV. But under the condition of pH 6.5, the size and CMC showed an increasing trend. Doxorubicin (DOX), a model anticancer drug, was efficiently loaded into mPEG-St-DCA micelles, and in vitro release exhibited that DOX-loaded micelles had a good in vitro pH-induced drug release. MTT assays confirmed that mPEG-St-DCA micelles were biocompatible with HeLa cells, and DOX-loaded micelles had a relatively better cytotoxicity against HeLa cells with a remarkably high IC50 of 5.74 μg mL−1. Confocal laser scanning microscopy (CLSM) analyses demonstrated that mPEG-St-DCA micelles could be internalized efficiently by HeLa cells to realize intracellular DOX release, which further enhanced the inhibition of cell proliferation. On the basis of the above results, it was indicated that novel amphiphilic mPEG-St-DCA micelles with pH-response could be used as drug delivery carriers for cancer therapy.
研究领域:
生物材料学
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）