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ACS Appl Mater Interfaces. 2017 Oct 25;9(42):36675-36687. doi: 10.1021/acsami.7b13055. Epub 2017 Oct 13.

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

Author information

1
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, People's Republic of China.

Abstract

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 (hPCBE), for chemo-photodynamic dual therapy. The easily prepared hPCBE possess a bottom-up-constructed hydrophobic core h-P(CPTMA-co-BYMAI) (hPCB) 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, hPCBE exists as unimolecular micelles in aqueous solution and exhibits excellent structural stability under dilution condition. The hPCBE micelles can be effectively internalized by MCF-7 cells and release CPT triggered by the reductive milieu. In addition, photosensitizer moieties embedded in the hPCB core could generate singlet oxygen (1O2) effectively under irradiation, endowing hPCBE with the boosting of chemotherapeutic efficacy. As compared to the single chemotherapy of hyperbranched polyprodrug amphiphiles h-PCPTMA-b-POEGMA (hPCE) and photodynamic therapy of hyperbranched polyphotosensitizer amphiphiles h-PBYMAI-b-POEGMA (hPBE), hPCBE 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.

KEYWORDS:

chemo-photodynamic dual therapy; drug delivery; redox-responsive; unimolecular micelles; “bottom-up” strategy

PMID:
28968057
DOI:
10.1021/acsami.7b13055
[Indexed for MEDLINE]

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