Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer
Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer
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DOI：
10.1016/j.apsb.2017.10.004
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发表时间：
2018-07-01
影响因子：
14.5
通讯作者：
Yallapu, Murali M.
中科院分区：
文献类型：
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作者：
Chowdhury, Pallabita;Nagesh, Prashanth K. B.;Yallapu, Murali M.
本研究的目的是开发和证明聚合物/紫杉醇自组装（PTX-SA）配方。使用动态光散射分析基于较小尺寸的制剂筛选聚合物/PTX-SA。此外，荧光显微镜和流式细胞术研究表明，基于聚乙烯吡咯烷酮（PVP）的PTX-SA（PVP/PTX-SA）在MCF 7和MDA-MB-231乳腺癌细胞中具有上级细胞内化能力。优化的PVP/PTX-SA对人红细胞表现出较低的毒性，表明其是用于降低全身毒性的合适制剂。通过荧光猝灭和透射电子显微镜证实了PVP和PTX自组装体的形成，透射电子显微镜（TEM）检测表明PVP/PTX-SA为球形，平均尺寸范围为53.81 nm。FTIR光谱分析表明PVP/PTX-SA中聚合物和紫杉醇官能团的掺入。使用增殖（MTS）和克隆形成（集落形成）测定来验证PVP/PTX-SA在乳腺癌细胞中相对于紫杉醇的上级抗癌活性。这种上级抗癌活性还通过促存活蛋白（Bcl-xL）表达的下调、凋亡相关蛋白（Bid、Box、裂解的半胱天冬酶7和裂解的PARP）的上调和β-微管蛋白稳定化来证明。这些结果支持PVP/PTX-SA改善紫杉醇递送至癌细胞的假设。(C)2018年中国药学会、中国医学科学院药物研究所。制作和主办：Elsevier B. V.
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.