Premium
Tumor Cells‐Selective Bionic Nanodevice Exploiting Heparanase Combats Metastatic Breast Cancer
Author(s) -
Lang Tianqun,
Ran Wei,
Dong Xinyue,
Zheng Zhong,
Liu Yiran,
Yin Qi,
Li Yaping
Publication year - 2018
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201707289
Subject(s) - heparanase , cancer research , cancer cell , metastasis , breast cancer , cancer , cytotoxicity , metastatic breast cancer , circulating tumor cell , nanomedicine , cytotoxic t cell , docetaxel , materials science , medicine , chemistry , nanotechnology , biochemistry , in vitro , nanoparticle
The clinical application of the cytotoxic chemotherapeutic agents in the treatment of metastatic breast cancer is limited by their poor selectivity to cancer cells. In this work, a bionic nanodevice consisting of the docetaxel (DTX)‐heparan sulfate (HS) conjugate (HS‐DTX) micelle with a red blood cells membrane (RBC) coating on its surface, termed as rHS‐DTX, is first constructed. It is found that the cytotoxicity of DTX is concealed by HS in human mammary epithelial Michigan Cancer Foundation (MCF)‐10A cells but restored in human mammary cancer MCF‐7 cells because HS is hydrolyzed by heparanase (Hpa), which is overexpressed only in MCF‐7 but not MCF‐10A cells. The RBC coating enhances the cellular uptake of HS‐DTX and endows it with the long circulating ability in blood. In the MCF‐7 metastatic breast cancer mice model, rHS‐DTX exhibits 6.35‐fold higher intratumor DTX accumulation than the free DTX injection and achieves a tumor inhibiting rate of 98.2% and a lung metastasis suppression rate of 99.6%. No severe toxicity is observed in the major organs and blood of mice treated with rHS‐DTX. In summary, rHS‐DTX can provide a promising strategy for targeting therapy of metastatic breast cancer by improving the tumor‐suppressing efficacy of DTX.