: Diabetes is a series of metabolic disorders that can be categorized into three types depending on different aspects associated with age at onset, intensity of insulin resistance, and beta- cell dysfunction: Type 1 and 2 Diabetes, and Gestational Diabetes Mellitus. Type 2 Diabetes Mellitus (T2DM) has recently been found to account for more than 85% of diabetic cases. The current review intends to raise awareness among clinicians/researchers that combining vitamin D3 with metformin may pave the way for better T2DM treatment and management. An extensive literature survey was performed to analyze vitamin D’s role in regulating insulin secretion, their action on the target cells and thus maintaining the normal glucose level. On the other side, the anti-hyperglycemic effect of metformin as well as its detailed mechanism of action was also studied. Interestingly both compounds are known to exhibit the antioxidant effect too. Literature supporting the correlation between diabetic phenotypes and deficiency of vitamin D was also explored further. To thoroughly understand the common/overlapping pathways responsible for the antidiabetic as well as antioxidant nature of metformin and vitamin D3, we compared their antihyperglycemic and antioxidant activities. With this background, we are proposing the hypothesis that it would be of great interest if these two compounds could work in synergy to better manage the condition of T2DM and associated disorders.

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.