Recent Advances in Organelle-Targeted Drug Delivery: Precision Medicine at the Subcellular Level.

Organelle-targeted drug delivery (OTDD) is an advanced strategy in the field of precision medicine, which delivers therapeutic agents to subcellular organelles. The OTDD provides a more targeted and efficient approach for neurodegenerative, cancer, and metabolic disorders, by addressing the root cause of diseases that are associated with organelle dysfunction. The recent advances in nanotechnology have enabled intelligent drug carriers, which have the potential to target organelles. This study aimed to explore the recent advancements in OTDD, emphasizing the role of nanocarriers, targeting approaches, and stimulus-responsive systems to enhance therapeutic accuracy and overcome major challenges in clinical translation. This review discusses advanced progress in OTDD, focusing on various nanocarriers. It discusses the function of targeting moieties, including peptides and ligands, as well as stimuli-responsive drug delivery systems that are activated by intracellular stimuli, like pH or reactive oxygen species, capable of targeting the delivery of the drug using organelles. Moreover, challenges in clinical translation, regulatory issues, and patient-specific factors are analyzed. OTDD advancements have shown promising preclinical and clinical outcomes in enhancing drug targeting and therapeutic efficiency. However, its clinical use involves barriers in standardization, regulatory approvals, and disease-specific variation, which primarily hinder its clinical application. Personalized strategies need to be employed to enhance the outcome of therapy. The OTDD has the potential to revolutionize subcellular precision medicine by providing specific drugs for different diseases. Interdisciplinary collaboration is required to address the existing challenges and facilitate clinical translation, thereby improving patient- specific therapeutic approaches.