摘要
To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL;hence, they are ideal carriers for low-dose antineoplastic drugs.
To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic~? F-127, which binds folic acid(FA), Pluronic~? F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL; hence, they are ideal carriers for low-dose antineoplastic drugs.
作者
YIN Meizhen
YU Xin
尹美珍;SU Zhenhong;CUI Bingcun;HAN Yingchao;DAI Honglian;喻昕(School of Medicine,Hubei Polytechnic University,Huangshi 435003,China;School of Medicine,Inner Mongolia University for Nationalities,Inner Mongolia Tongliao 028000,China;State Key Laboratory of Advanced Technology for Materials Synthesis and Processing,and Biomedical Materials and Engineering Center,Wuhan University of Technology,Wuhan 430070,China)
基金
Funded by the National Natural Science Foundation of Hubei Province(No.2014CFB306)
the National Natural Science Foundation of China(No.51772233)
the National Key Research and Development Program of China(No.2016YFC1101605)
the Science and Technology Support Program of Hubei Province(No.2015BAA085)