HSPA1A-siRNA nucleated gold nanorods for stimulated photothermal therapy through strategic heat shock to HSP70

Abstract

Herein, we report the surface modification of gold nanorods (GNRs) with siRNA and mPEG to prepare hot plasmonic mPEG@siRNA@GNR nano-assemblies for highly efficient photothermal therapy. mPEG embedding after siRNA coating on the GNRs increases the colloidal stability of mPEG@siRNA@GNRs and leads to a red-shift of the LSPR band along with peak broadening which increases the 808 nm NIR light absorption to around 56%. A very low concentration of the prepared nanostructures enhanced the photothermal temperature to 53.4 °C with 2 W of laser power density. The prepared nanostructure showed easy intracellular uptake without significant cytotoxicity for murine colorectal carcinoma cells (CT26). The gene-silencing efficiency of mPEG@siRNA@GNRs significantly reduced hyperthermal induced-HSP70 protein expression. When treated with mPEG@siHSPA1A@GNRs and NIR, the expression of HSP70 was diminished by siRNA of the HSPA1A gene and the CT26 cancer cells became more sensitive to mPEG@siHSPA1A@GNRs. The JC-1 and MitoSox staining results showed that NIR irradiated mPEG@siHSPA1A@GNRs induced apoptotic cell death which triggered the distribution of the mitochondrial membrane potential and induction of superoxide production. Furthermore, the apoptotic cell death was related to BAX protein expression by the silencing effect of siRNA for HSP70. These results provide an anti-cancer nano-platform for the combination therapy of NIR-triggered hyperthermal treatment and strategic HSPA1A gene silencing against HSP70.