Polyion Complex Vesicles for Photoinduced Intracellular Delivery of Amphiphilic Photosensitizer
Polyion Complex Vesicles for Photoinduced Intracellular Delivery of Amphiphilic Photosensitizer
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用于光诱导细胞内递送两亲性光敏剂的聚离子复合囊泡
DOI：
10.1021/ja406992w
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发表时间：
2014-01-08
影响因子：
15
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Chen, Huabing;Xiao, Ling;Kataoka, Kazunori
由一对带相反电荷的聚乙二醇（PEG）基嵌段异构体和同位异构体形成的聚合物囊泡，称为“PICsomes”，具有可调节的大小，并且由于多离子络合物（PIC）膜的柔性和可调节的亲水性而具有独特的半透性。通过简单的溶液涡旋混合，PICsomes可以将多种分子封装在水相内部，有望成为具有生物医学意义的物质的纳米容器。在这里，我们报道了picsome的一种新功能：光诱导释放光活性药物用于细胞内药物递送。一种强效光敏剂Al（III）酞菁二磺酸（AlPcS2a）被有效地掺入到picsome中（11%(w/w)），其快速释放可能是由于piga膜的光化学损伤引起的。高分辨率荧光共聚焦显微镜和溶酶体膜特异性染色方法的结合显示，即使在活细胞内吞后的溶酶体中，也会发生AlPcS2a的光诱导释放。同时，释放的AlPcS2a光化学影响溶酶体膜的完整性，导致AlPcS2a和picsome自身易位到细胞质中。因此，包裹AlPcS2a的picsome （aipcs2a - picsome）表现出明显比单独的游离AlPcS2a更强的光细胞毒性。因此，alpcs2a - picsome在光动力治疗或光诱导治疗分子的细胞质递送方面具有良好的可行性。
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 photoirracliation possibly due to the photochemical damage of the PIG 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 (AIPcS2a-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.