IF-7 and GALA modified PEG-PDMAEMA loaded SOX10 siRNA nanoparticles: Preparation, cellular delivery, and inhibition on progression of triple negative breast cancer and its bone metastasis in vitro

SRY-related high-mobility-group box 10 (SOX10) is reported to be a sensitive lineage marker in primary and metastatic triple negative breast cancer (TNBC). However, there has no exploration in the delivery of SOX10 small interfering RNA (siRNA) to treat TNBC. Poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PDMAEMA) modified with peptides IF-7 and GALA was employed to assemble SOX10 siRNA into nanoparticles. The results revealed that the prepared nanoparticles were was regularly round with uniform sizes of about 102.9 +/- 1.93 nm, exhibiting good stability and pH-triggered release profile at pH 5.0. The nanoparticles were efficiently uptaken by MDA-MB-231 cells via cholesterol dependent, caveolae- and clathrin-mediated endocytosis and escaped from lysosomes. The nanoparticles inhibited proliferation, invasion and migration of MDA-MB-231 cells, as well as chemotactic migration, heterogeneous adhesion and anchorage-independent growth of MDA-MB-231 cells in simulated bone microenvironment. The nanoparticles inhibited the mRNA and protein expression of SOX10, subsequently inhibited Nestin, beta-catenin, c-Myc and CyclinD1 expression. The effect of the nanoparticles on TNBC and its bone metastasis might attribute to the blockade of Nestin and Wnt/beta-catenin pathway after the silencing of SOX10. Taken together, IF-7 and GALA modified PEG-PDMAEMA loaded SOX10 siRNA nanoparticles provide a new strategy to treat TNBC and its bone metastasis.