期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 48, 页码 44961-44969出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b15996
关键词
photodynamic therapy; GSH activatable; cyanine; mitochondria targeting; near infrared
资金
- National Natural Science Foundation of China [21574039, 21875063]
- Shanghai Sailing Program [19YF1410900]
Developing smart photosensitizers that are sensitive to tumor-specific signals for minimal side effects and enhanced antitumor efficacy is a tremendous challenge for tumor phototherapies. Herein, we construct a nanoplatform with glutathione (GSH)-activatable and mitochondria-targeted pro-photosensitizer encapsulated by ultrasensitive pH-responsive polymer for achieving imaging-guided tumor-specific photodynamic therapy (PDT). The GSH-activatable pro-photosensitizer, di-cyanine (DCy7), has been synthesized where two cyanine moieties are covalently conjugated by a disulfide bond, and the hydrophobic DCy7 is further encapsulated with an amphiphilic pH-responsive diblock copolymer POEGMA-b-PDPA to form P@DCy7 nanoparticles. Upon endocytosis by cancer cells, P@DCy7 nanoparticles dissociate at endosome first and then DCy7 is released to cytoplasm and subsequently activated by the high concentration of GSH, finally targets mitochondria for organelle-targeted PDT. Moreover, intracellular antioxidant GSH is consumed during the activation procedure that is beneficial to efficient PDT. These P@DCy7 nanoparticles display selective phototoxicity against tumor cells (HepG2 or 4T1 cells) over normal cells (BEAS-2B cells) in vitro, and their GSH-activatable enhanced PDT efficacy is further confirmed in tumor-bearing mice. Thus, P@DCy7 nanoparticles allow for accurate and highly efficient PDT with minimal side effects, providing an attractive nanoplatform for organelle-targeted precise PDT.
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