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| Polymeric Nanomicelles Conjugated with BODIPY-based Photosensitizers for Targeted Photodynamic Therapy |
| ZHOU Zhong-ting1, ZHANG Quan1,2, WANG Sheng-tao1, CAI Yin1, NAKANISHI Hideki1,2, YIN Jian1,2 |
1. Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China;
2. School of Biotechnology, Jiangnan University, Wuxi 214122, China |
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Abstract Objectives:Polymeric nanomicelles have attracted more attention since it could become a targeted delivery system of photosensitizers for cancer photodynamic therapy (PDT). Methods:The poly(butyl acrylate)-block-poly(glycidyl methacrylate) (PtBA-b-PGMA) copolymer was first synthesized by atom transfer radical polymerization. After the tert-butyl group was removed from PtBA-b-PGMA, mannose was covalently linked via amide reaction. Finally, BODIPY-based photosensitizers were introduced by the "click" reaction to obtain polymeric nanomicelles (Man-PAA-b-PGMA-BPDIPY). Structure of Man-PAA-b-PGMA-BPDIPY was confirmed by 1H NMR and FT-IR. The size and morphology of Man-PAA-b-PGMA-BODIPY was characterized by transmission electron microscopy and dynamic light scattering. The cytotoxicity, cellular uptake and PDT effects of Man-PAA-b-PGMA-BODIPY were investigated by MTT assay and confocal laster scanning microscope. Results:The relative molecular weight of PtBA-b-PGMA is 16 924, and the dispersion coefficient is 1.36. The appearance of a peak at 2 106 cm-1 in the FTIR spectrum of Man-PAA-b-PGMA-N3 indicates successful grafting of azide groups onto the polymer. This peak disappeared and a new peak at 1 637 cm-1 was observed after azide-alkyne cycloaddition "click" chemistry, indicating the formation of triazole bonds in Man-PAA-b-PGMA-BODIPY. Polymeric nanomicelles have uniform size distribution and excellent stability in aqueous solution. The average hydrodynamic diameter of polymeric nanomicelles is 178 nm with a narrow size distribution (PDI=0.298). Man-PAA-b-PGMA-BODIPY did not exhibit toxicity against MDA-MB-231 and HEK293 cells in the dark, while the enhanced phototoxicity was observed on MDA-MB-231 cancer cells under 535 nm LED irradiation. Conclusions:Man-PAA-b-PGMA-BODIPY was efficiently internalized by MDA-MB-231 cancer cells through receptor-mediated endocytosis, while HEK293 normal cells showed much lower endocytosis towards micelles under the same conditions. Thus, Man-PAA-b-PGMA-BODIPY shows its potential for targeted PDT of cancer.
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Received: 07 April 2017
Published: 25 October 2017
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