Dendrimers in cancer therapy: emerging clinical design strategies

Dendrimers are highly branched synthetic polymers whose well-defined architecture enables high drug loading and payload protection. However, their clinical translation in oncology has been hindered by systemic toxicity, inefficient tumor targeting, and premature drug release. To overcome these barriers, recent advances have converged on three integrated design strategies: surface modification and biodegradable backbones to ensure safety; physicochemical tuning and ligand conjugation to enhance tumor targeting; and stimuli-responsive linkers to enable controlled drug release. The clinical progress of DEP-SN38 (DEP, dendrimer-nanoparticle delivery platform) (Starpharma Holdings), a dendrimer-drug conjugate, exemplifies the successful translation of these principles. In this review, we discuss these strategies and analyze how their interplay addresses key clinical challenges, with a focus on their relevance to ongoing and future clinical development.