期刊
ACTA PHARMACEUTICA SINICA B
卷 8, 期 4, 页码 602-614出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2017.10.004
关键词
Drug delivery; Nanoparticles; Self-assemblies; Polymer; Cancer therapeutics; Breast cancer
资金
- National Institute of Health/National Cancer Center's Career Development Award [K22 CA174841, R15 CA 213232]
- National Institutes of Health Research Project [R01 CA210192, R01 CA206069, CA204552]
- UTHSC-College of Pharmacy-Dean's Seed Grant
- NATIONAL CANCER INSTITUTE [R01CA204552, K22CA174841, R01CA210192, R15CA213232, R01CA206069] Funding Source: NIH RePORTER
The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an average size range of 53.81 nm as detected by transmission electron microscopy (TEM). FTIR spectral analysis demonstrates incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both proliferation (MTS) and clonogenic (colony formation) assays were used to validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over paclitaxel. Such superior anticancer activity was also demonstrated by downregulation of the expression of pro-survival protein (Bcl-xL), upregulation of apoptosis-associated proteins (Bid, Box, cleaved caspase 7, and cleaved PARP) and beta-tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells. (C) 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据