A mitochondrial-targeted nanomedicine based on hollow mesoporous silica nanoparticles for enhanced colorectal cancer therapy

By focusing on mitochondria as a therapeutic target, strategies can be devised to deplete ATP levels, thereby potentially circumventing the emergence of MDR. In this study, we developed a surface-modified hyaluronic acid (HA), mitochondrial targeted hollow mesoporous silicon nanomedicine (PB@HMSN-HA) co-loaded with berberine (BBR) and paclitaxel (PTX) for enhanced colorectal cancer therapy. The modified HA can selectively bind to tumor cells that overexpress the CD44 receptor, leading to the accumulation of PB@HMSN-HA at the tumor site and improving tumor targeting efficiency. After cellular internalization, the liberated positively charged BBR, which is specifically targeted to mitochondria, induces a reduction in ATP levels. Depletion of ATP subsequently results in a reduction of drug efflux, thereby amplifying the antitumor efficacy of PTX. Therefore, this combination therapy strategy targeting mitochondria serves as an important reference for clinical oncological chemotherapy. • A mitochondrial-targeted nanomedicine is proposed for enhanced cancer therapy. • Enhanced tumor targeting is achieved by the interaction of hyaluronic acid with CD44 receptor. • Nanomedicine facilitates the targeted delivery of berberine to mitochondria. • Berberine induces an increase in intracellular reactive oxygen species and a decrease in ATP levels. • Decreased ATP levels can inhibit drug efflux, thereby potentiating the antitumor efficacy.