Emerging small molecule-engineered hybrid nanomedicines for cancer therapy

Cancer should not be simply regarded as a single disease, but an intricate adaptive system involved with inflammation, metabolism and immunization. Therefore, combination of two or more antineoplastic drugs reveals distinct advantages over monotherapy. However, despite the rapid development of biomedical nanotechnology, it remains challenging to precisely co-deliver multiple drugs into tumors, owing to the differences between the compatibility of different drugs and nanomaterials. Many efforts have been devoted to developing new nanodrug delivery systems (NDDS). In recent years, carrier-free nanoassemblies engineered by small molecules have emerged as a promising and versatile nanoplatform for co-delivery of anticancer drugs. Given the rapid progress in carrier-free small-molecule hybrid nanoassemblies, we here provide an overview on the latest updates in this emerging field. First, the recent trends in nanomedicines engineered by pure drugs and/or prodrugs are summarized. Then, the underlying assembly mechanisms and drug release characteristics are briefly analyzed. Finally, the prospects and challenges of hybrid nanoassemblies in clinical translation are highlighted.