Mitochondria are the key energy provider to highly proliferating cancer cells, and are subsequently considered one of the critical targets in cancer therapeutics. Several compounds have been studied for their mitochondria-targeting ability in cancer cells. These studies’ outcomes have led to the invention of “mitocans”, a category of drug known to precisely target the cancer cells’ mitochondria. Based upon their mode of action, mitocans have been divided into eight classes. To date, different synthetic compounds have been suggested to be potential mitocans, but unfortunately, they are observed to exert adverse effects. Many studies have been published justifying the medicinal significance of large numbers of natural agents for their mitochondria-targeting ability and anticancer activities with minimal or no side effects. However, these natural agents have never been critically analyzed for their mitochondria-targeting activity. This review aims to evaluate the various natural agents affecting mitochondria and categorize them in different classes. Henceforth, our study may further support the potential mitocan behavior of various natural agents and highlight their significance in formulating novel potential anticancer therapeutics.

The technique of gene therapy, ever since its advent nearly fifty years ago, has been utilized by scientists as a potential treatment option for various disorders. This review discusses some of the major neurodegenerative diseases (NDDs) like Alzheimer’s disease (AD), Parkinson’s Disease (PD), Motor neuron diseases (MND), Spinal Muscular Atrophy (SMA), Huntington’s Disease (HD), Multiple Sclerosis (MS), etc. and their underlying genetic mechanisms along with the role that gene therapy can play in combating them. The pathogenesis and the molecular mechanisms specifying the altered gene expression of each of these NDDs have also been discussed in elaboration. The use of gene therapy vectors can prove to be an effective tool in the field of curative modern medicine for the generations to come. Therefore, consistent efforts and progressive research towards its implementation can provide us with powerful treatment options for disease conditions that have so far been considered as incurable.

Mitochondria are central regulators of cancer cell survival, metabolism, and therapy resistance, making them a promising yet underutilized target in modern oncology. Internal stimuli such as altered redox balance, elevated reactive oxygen species (ROS), and acidic pH uniquely characterize the tumor microenvironment, providing a distinct trigger for smart drug delivery. Internal stimuli-responsive nanocarriers have emerged as an innovative strategy to achieve spatiotemporal control of drug release while selectively homing to subcellular organelles such as mitochondria. This review outlines the multifaceted role of mitochondria in cancer progression, chemoresistance, and metastasis, and highlights the unique biochemical hallmarks of cancer cells that facilitate targeted delivery. We further explore recent advances in the development of pH-, redox-, ROS-, and enzyme-sensitive nanocarriers that exploit these internal cues to localize chemotherapeutic agents specifically to cancerous mitochondria. We also compare their advantages and limitations with conventional chemotherapy and other targeting approaches. Additionally, translational challenges, limitations, and future directions including vesicle-mediated mitochondria transfer are discussed, aiming to reduce systemic toxicity while improving therapeutic efficacy.