Enhancing therapeutic effects of docetaxel-loaded dendritic copolymer nanoparticles by co-treatment with autophagy inhibitor on breast cancer.
Enhancing therapeutic effects of docetaxel-loaded dendritic copolymer nanoparticles by co-treatment with autophagy inhibitor on breast cancer.
复制标题
负载多西他赛的树枝状共聚物纳米粒子与自噬抑制剂联合治疗增强乳腺癌的治疗效果
作者：
Zhang X;Yang Y;Liang X;Zeng X;Liu Z;Tao W;Xiao X;Chen H;Huang L;Mei L
树枝状聚合物是合成纳米载体，包含高度支化的球形聚合物，作为新的、有效的药物输送工具。然而，纳米载体被细胞内化后的命运却很少被研究。制备了负载多西紫杉醇的树枝状共聚物H40-聚(D,L-丙交酯)纳米颗粒，称为“DTX-H40-PLA NPs”，并用作评估NPs是否被自噬隔离并与溶酶体融合的模型。除了通过内溶酶体途径降解外，负载 DTX 的 H40-PLA NP 还被自噬体隔离并通过自溶酶体途径降解。负载 DTX 的 H40-PLA NP 在诱导人类 MCF-7 癌细胞自噬后可能会停止发挥有益作用。通过树突状共聚物纳米颗粒共同递送自噬抑制剂（如氯喹）和化疗药物 DTX，大大增强了体外对癌细胞的杀伤力，并减少了严重联合免疫缺陷小鼠的肿瘤体积和重量。这些发现为纳米医学的发展提供了宝贵的证据，例如用于临床应用的树枝状共聚物纳米粒子。
Dendrimers are synthetic nanocarriers that comprise a highly branched spherical polymer as new, efficient tools for drug delivery. However, the fate of nanocarriers after being internalized into cells has seldom been studied. Docetaxel loaded dendritic copolymer H40-poly(D,L-lactide) nanoparticles, referred to as “DTX-H40-PLA NPs”, were prepared and used as a model to evaluate whether the NPs were sequestered by autophagy and fused with lysosomes. Besides being degraded through the endolysosomal pathway, the DTX-loaded H40-PLA NPs were also sequestered by autophagosomes and degraded through the autolysosomal pathway. DTX-loaded H40-PLA NPs may stop exerting beneficial effects after inducing autophagy of human MCF-7 cancer cells. Co-delivery of autophagy inhibitor such as chloroquine and chemotherapeutic drug DTX by dendritic copolymer NPs greatly enhanced cancer cell killing in vitro, and decreased both the volume and weight of the tumors in severe combined immunodeficient mice. These findings provide valuable evidence for development of nanomedicine such as dendritic copolymer NPs for clinical application.
登录
查看更多内容
影响因子：
14
作者：
Li, Jasmine J.;Hartono, Deny;Yung, Lin-Yue L.
通讯作者：
Yung, Lin-Yue L.
影响因子：
6.4
作者：
Taylor, C. R.;Levenson, R. M.
通讯作者：
Levenson, R. M.
影响因子：
78.5
作者：
Mathew, Robin;Karantza-Wadsworth, Vassiliki;White, Eileen
通讯作者：
White, Eileen
影响因子：
12.4
作者：
Muthu MS;Leong DT;Mei L;Feng SS
通讯作者：
Feng SS
DOI：
10.1038/nrc3262
发表时间：
2012-04-26
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--