Ionizable Mesoporous Silica Nanoparticles Mediated siAURKB Delivery for Colorectal Cancer Therapy

Abstract

Colorectal cancer (CRC) is a common malignant tumor with high incidence and mortality worldly. Conventional therapeutic strategies, such as surgical resection and chemotherapy showing improved outcomes for partial patients, are greatly hindered by drug resistance and off-target toxicity. Small interfering RNA (siRNA)-mediated RNA interference provides a breakthrough for precision CRC therapy. However, efficient delivery of siRNA to the tumor site with complex tumor microenvironment remains challenging. Here, an ionizable mesoporous silica nanoparticle (MSN) based nanocarrier with high siRNA loading capacity and enhanced cell membrane penetration capability is developed for effective CRC therapy. By modifying diethylamino groups on the surface of MSNs featured with maze-like pores, a new siRNA delivery carrier denoted MPMNC is successfully prepared, which exhibits improved cellular uptake efficiency in CT26 cells and significant fluorescence silencing effect in EGFP-293T cells. Furthermore, aurora-B siRNA (siAURKB) that downregulates the expression of AURKB in tumor cells to induce apoptosis is loaded onto MPMNC to afford siAURKB@MPMNC nanomedicine, which delivers siAURKB to tumor cells and inhibits the tumor growth effectively with a tumor growth inhibition rate of 64.9% through intratumor injection in CRC model mice. Meanwhile, it exhibits excellent biocompatibility in vitro and in vivo. Overall, this work presents a novel siAURKB-loaded MSN nanomedicine highlighting the surface modification with ionizable amino groups, offering a promising CRC therapy paradigm.