Targeted nanomedicine in cisplatin-based cancer therapeutics

Since its license in 1978, cisplatin has proved to be one of the most successful chemotherapeutic agents in the world. However, two acute challenges facing cisplatin, resistance and toxicity, have resulted in a bottleneck of clinical application. Targeted nanomedicine shows great promise in delivering cisplatin for maximizing efficacy while minimizing off-target toxicity. This article surveyed the recent progress and challenges of targeted nanomedicine in managing resistance and toxicity of cisplatin in both fundamental and clinical aspects. Particularly, we focused on three major mechanisms counteracting cisplatin sensitivity (decreased intracellular accumulation, increased cisplatin deactivation, and enhanced DNA repair/translesion synthesis) and correspondingly highlighted a few representative approaches to increase cisplatin sensitivity through improving the intracellular concentration of cisplatin and implementing combination therapy. Moreover, the requirements for future advancements in cisplatin delivery systems are rendered with emphasis on (i) understanding of nano-bio interaction and post-accumulation biological effects instead of overwhelmingly improving tumor accumulation, (ii) development of stimuli-responsive and/or actively-targeted nanomedicines, (iii) optimization of combination therapy, (iv) novel combinations targeting tumor microenvironment and immunotherapy. We postulate that cisplatin-based nanomedicines will continuously advance and potentially revolutionize oncological treatment.