A supramolecular co-delivery strategy for combined breast cancer treatment and metastasis prevention

We herein propose a co-delivery approach where small interference RNA (siRNA) and anticancer chemotherapeutic drug are simultaneously loaded into a single delivery carrier for the combined treatment of breast cancer and metastasis prevention. The co-delivery vector is composed of chondroitin sulfate (CS)-coated beta-cyclodextrin-polyethylenemine polymer, which is capable of loading paclitaxel (PTX) and siRNA simultaneously to form therapeutic nanocomplexes. The nanocomplex, termed as CPPTX-siCD146-CS, is demonstrated to have strong active targeting ability towards CD44-overexpresing breast cancer cells. Moreover, the co-delivery of PTX and siRNA not only effectively inhibits cancer cells proliferation and induces apoptosis, but also well prevents metastasis. Importantly, CP-PTX-siCD146-CS nanocomplexes exhibit stronger cytotoxic effects and anti-metastatic effects on MBA-MD-231 breast cancer cells, in comparison with PTX or siCD146 mono-treatment. The current study defines a potential therapeutic strategy for the combined breast cancer treatment and metastasis prevention from a codelivery perspective. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.