Carrier-free nanomedicines: Mechanisms of formation and biomedical applications

In recent years, significant advancements in nanotechnology have yielded remarkable improvements in biomedical applications. Nanocarriers, harnessed from the principles of nanotechnology, have garnered widespread utilization in medicine delivery and diagnostics. However, the progression of nanocarriers has been hindered by two key challenges: low drug loading capacity and the potential for carrier-induced toxicity. To surmount these obstacles, the rapid development and expansion of carrier-free drug delivery systems (CFDDSs) composed of pure drugs and prodrugs have emerged as a promising solution. Extensive endeavors have been undertaken to explore novel excipients, therapeutic agents, self-assembly processes, and therapeutic mechanisms, aimed at expanding the horizons of CFDDSs and enhancing their therapeutic efficacy. This comprehensive review provides an overview of CFDDSs, elucidating their self-assembly mechanisms. Additionally, we examine their diverse biomedical applications while shedding light on the challenges ahead for the future development and clinical implementation of CFDDSs. This review serves to enhance our understanding of the intricate mechanisms governing drug nanoassembly formation and fosters the advancement of CFDDSs in the expansive realm of biomedical research.