Nanomaterial-driven drug repositioning: design strategies, regulatory mechanisms, and biomedical applications

Drug repositioning, defined as the identification and development of new therapeutic applications for existing drugs, has attracted considerable attention due to its advantages of low cost, reduced risk, and high efficiency. Driven by the continuous and accelerated advancement of nanotechnology, nanomaterial-driven drug repositioning, integrating the advantages of the drug repositioning concept and the delivery potential of nanosystems, has offered a highly safe and effective route for disease management. In this review, we aim to highlight and discuss the recent representative investigations involving nanomaterials for drug repositioning, mainly emphasizing the nanomaterial design approaches for drug repositioning, including nanocarrier-mediated single-drug delivery, nano-enabled synergistic co-delivery, active ingredient optimization, and nanomaterials acting as active therapeutic agents. Next, we summarize the biological performance regulatory mechanisms in nanomaterial-driven drug repositioning centered on pharmacokinetic behavior, pharmacodynamic behavior, synergistic therapeutic potential, and toxicological profile. We also underline the promising applications based on nanomaterials for drug repositioning against neurodegenerative and cerebrovascular diseases, malignant tumors, inflammatory and infectious diseases, cardiovascular diseases, tissue engineering, and other illnesses. Additionally, we outline the main obstacles and future perspectives of nanomaterial-driven drug repositioning, primarily focusing on the possibilities and challenges in clinical translation. Furthermore, we hope that the review will bring new opportunities for nanomedicines based on drug repositioning, thus promoting the progress and advancement of new drug development.