Recent Advances in Mitochondria-Targeted Nano-Drug Delivery Systems for Cancer Therapy

Abstract: Cancer remains a major disease that poses a serious threat to human health. Conventional treatments such as radiotherapy, chemotherapy, and surgery are limited by systemic toxicity and tumor recurrence, which hinder the achievement of highly efficient and specific therapy. The development of nanodrug delivery systems has provided new opportunities for cancer treatment. Utilizing mechanisms such as passive targeting (eg, the EPR effect) and active targeting (eg, peptide-based surface modification), these systems can precisely deliver drugs to tumor sites, thereby significantly reducing systemic toxicity. In recent years, research focus has shifted from tissue-level targeting to subcellular organelle targeting, particularly of mitochondria. Functioning as cellular power plants, mitochondria are deeply involved in tumor initiation, progression, and the regulation of apoptosis, making them important targets for cancer therapy. Based on the structural features of mitochondria and their dysfunctional role in cancer, this review systematically explores strategies for mitochondria-targeted nanodrug delivery and summarizes the latest research advances along with future directions in cancer treatment. A unique aspect of this review is its systematic integration of the design principles from mitochondrial substructure characteristics to multi-level targeting strategies, underscoring the innovative potential of nanocarriers in overcoming tumor drug resistance and enabling precise intervention. This work thereby provides a theoretical basis and novel insights for precision oncology. Keywords: nano-drug delivery carriers, mitochondrial targeting, tumor microenvironment, responsive nanocarriers