Subcellular Organelle Targeting of Mitochondria Using Nanomedicines: Cancer Therapeutics and Theranostics Potential

Nanomedicines are rapidly evolving in chemotherapy and image-guided theranostics for specific and controlled delivery of the target therapeutic molecule. Targeting the subcellular organelles of cancer cells has gained focus in the recent decade for precise targeting of cancer cells and the activation of specific cancer death pathways. This strategy also overcomes the limitations of conventional chemo and radiation therapies, such as non-specificity and toxicity to the surrounding healthy tissue. Diverse roles of mitochondria in cancer, including oxidative stress signaling, metabolic reprogramming, cell death evasion, and cell survival mechanism, make it a promising target for cancer therapy. However, targeting mitochondria is tedious due to its complex structure and strong negative membrane potential. Various studies have designed mitochondria specific inorganic-, polymer-, dendrimer-, peptide- and protein-based nanoformulations to overcome barriers in targeting mitochondria of cancer cells. In this review, we have summarized the recently developed mitochondria-targeted nanoformulations in the field of chemotherapy, imageguided phototherapy, and combinatorial therapies. These nanoformulations showed enhanced cell penetration and mitochondrial accumulation of the drug molecules. In vitro and in vivo studies have shown promising results and further pre-clinical and clinical studies are required to develop these nanoformulations as effective cancer therapy.