“Bottom-Up” Construction of Hyperbranched Poly(prodrug-co-photosensitizer) Amphiphiles Unimolecular Micelles for Chemo-Photodynamic Dual Therapy

Despite the great advantages of chemo-photodynamic combination therapy, tedious synthesis steps and laborious purification procedures make the fabrication of chemo-photodynamic combined therapeutic platforms rather difficult. In this study, we develop a facile “bottom-up” strategy to fabricate hyperbranched poly(prodrug- co -photosensitizer) amphiphiles, h -P(CPTMA- co -BYMAI)- b -POEGMA ( h PCBE), for chemo-photodynamic dual therapy. The easily prepared h PCBE possess a bottom-up-constructed hydrophobic core h -P(CPTMA- co -BYMAI) ( h PCB) direct copolymerized from reduction-responsive CPT prodrug monomer (CPTMA) and boron dipyrromethene-based photosensitizer monomer (BYMAI), as well as a biocompatible shell polymerized from hydrophilic monomers. Because of the covalently interconnected core–shell structure, h PCBE exists as unimolecular micelles in aqueous solution and exhibits excellent structural stability under dilution condition. The h PCBE micelles can be effectively internalized by MCF-7 cells and release CPT triggered by the reductive milieu. In addition, photosensitizer moieties embedded in the h PCB core could generate singlet oxygen ( 1 O 2 ) effectively under irradiation, endowing h PCBE with the boosting of chemotherapeutic efficacy. As compared to the single chemotherapy of hyperbranched polyprodrug amphiphiles h -PCPTMA- b -POEGMA ( h PCE) and photodynamic therapy of hyperbranched polyphotosensitizer amphiphiles h -PBYMAI- b -POEGMA ( h PBE), h PCBE shows higher in vitro cytotoxicity. We expect that our approach will further boost research on the design of multifunctional drug delivery systems via the facile “bottom-up” strategy.