Targeting Mitochondria in Cancer Cells Using Nano Platforms

Abstract

Cancer is one of the leading causes of morbidity and mortality worldwide. To understand the characteristics of cancer cells, the hallmarks of cancer are outlined by Hanahan and Weinberg. Resisting cell death and deregulation of cellular energetics are the two imperative hallmarks of cancer which are tightly governed by an important sub-cellular organelle, mitochondrion. The mitochondrion is known to be "the power house of the cell" since it produces energy in the form of ATP. Although, mitochondria is called "the power house of the cell", its roles in cancer progression are very well highlighted in recent studies and made it an alternative and interesting target for cancer therapy. However, there are three major challenges in targeting mitochondria in next generation cancer therapy: (a) selective targeting of mitochondria in cellular milieu, (b) specific targeting of mitochondria in cancer tissues and (c) overcome drug resistance. To address these, we have developed lipidic nanoparticle for specific targeting of Bcl-2 protein on mitochondria in cancer cells to overcome drug resistance. Moreover, we also developed Cerberus and graphene oxide based nanoplatforms to target the mitochondrial DNA and associated proteins in cancer cells. Furthermore, mitochondria show complex cross-talk with the nucleus and endoplasmic reticulum(ER) for protein and lipid supply. Hence, simultaneous targeting of nucleus and mitochondria would lead to the augmented therapeutic outcome. To address this, we have developed dual-drug conjugated nanoparticles to target nucleus and mitochondria in cancer cells. We envision that the here presented unique approaches can be easily translated into clinics as platform technologies to inhibit multiple diverse targets concurrently into mitochondria, improve the therapeutic efficacy, reduce the off-target toxicity, overcome drug resistance and finally, offer a better quality of life to the cancer patients.