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Polyion complex vesicles for photoinduced intracellular delivery of amphiphilic photosensitizer

, : Polyion complex vesicles for photoinduced intracellular delivery of amphiphilic photosensitizer. Journal of the American Chemical Society 136(1): 157-163

Polymer vesicles formed by a pair of oppositely charged poly(ethylene glycol) (PEG)-based block aniomer and homocatiomer, termed "PICsomes", have tunable size, and are characterized by unique semipermeable property due to the flexible and tunable hydrophilicity of polyion complex (PIC) membranes. The PICsomes can encapsulate a variety of molecules in an inner aqueous phase just by a simple vortex mixing of solution, expecting their utility as nanocontainers of substances with biomedical interests. Here, we report on a new functionality of the PICsomes: photoinduced release of photoactive agents for intracellular drug delivery. A potent photosensitizer, Al(III) phthalocyanine chloride disulfonic acid (AlPcS2a), was efficiently incorporated into the PICsomes (11%(w/w)), and its quick release was induced by photoirradiation possibly due to the photochemical damage of the PIC membranes. The combination of a high-resolution fluorescent confocal microscopy and a lysosome membrane-specific staining method revealed that such photoinduced release of AlPcS2a occurred even in the lysosomes of living cells after endocytic internalization. Simultaneously, the released AlPcS2a photochemically affected the integrity of the lysosomal membranes, leading to the translocation of AlPcS2a and PICsomes themselves to the cytoplasm. Consequently, the AlPcS2a-encapsulated PICsomes (AlPcS2a-PICsomes) exhibited appreciably stronger photocytotoxicity compared with free AlPcS2a alone. Thus, the AlPcS2a-PICsomes have promising feasibility for the photodynamic therapy or the photoinduced cytoplasmic delivery of therapeutic molecules.


PMID: 24283288

DOI: 10.1021/ja406992w

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