Engineering the Hydrophilic–Hydrophobic\nInterface\nof Polymeric Micelles by Cationic Blocks for Enhanced Chemotherapy

The cationic surface charge critically influences the\nbiological\nfunctions and therapeutic outcomes of the cancer nanomedicines. However,\nthe basic correlation between the cationic group categories and their\ntherapeutic efficacy has not been elucidated. In this study, cationic\npolymeric nanoparticles with amino groups (primary, tertiary, and\nquaternary amines) as the single variable were leveraged to investigate\nthe various effects of amino species for enhanced antitumor chemotherapy.\nThe nanoparticles were constructed from a series of triblock polymers\nwith varying cationic repeating units at the hydrophilic–hydrophobic\ninterface. Our results suggested that quaternary ammonium outperforms\nits primary and tertiary counterparts in destroying mitochondrial\nmembranes to induce apoptosis, penetrating deep inside the tumor tissue,\nand damaging tumor vasculatures. As a result, we were able to effectively\ninhibit tumor growth in mice by a quaternary ammonium conjugate without\ncausing significant toxicity. Our work demonstrated that the chemical\nstructures played vital roles in regulating their biological functions\nand provided valuable information for designing cationic drug delivery\nsystems.