Carrier-free antitumor nanomedicines based on plant-derived compounds: From conceptual innovation to therapeutic potential.

Plant-derived compounds hold unique advantages in cancer treatment, owing to multi-target synergy and low toxicity, but their clinical translation is often hampered by poor water solubility and low bioavailability. Inspired by the booming innovations in nanotheranostics, formulating these compounds into nanomedicines has emerged as a promising solution. Carrier-free nanomedicines, formed through the self-assembly of drug molecules themselves, represent a cutting-edge research direction since a theoretically 100 % drug-loading ratio can be achieved and carrier-related safety concerns is eliminated by not using foreign inactive ingredients. This review summarizes recent progresses in this specific field, by categorizing the relevant nanomedicines mainly into mono-drug self-assemblies and multidrug co-assemblies. Particular emphasis has been placed on the assembly driving forces for different molecules to facilitate predictive nanoformulation design. Perspectives on the future developments are also given by outlining the critical challenges and potential solutions, and by answering the question of whether the carrier-free strategy is for recognition or for utility. It is anticipated that this overview can provide fundamental insights and catalyze innovative methodologies for the future design of plant-derived nanomedicines.