Selective photosensitizer delivery into plasma membrane for effective photodynamic therapy
Selective photosensitizer delivery into plasma membrane for effective photodynamic therapy
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DOI：
10.1016/j.jconrel.2014.05.049
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发表时间：
2014-10-10
影响因子：
10.8
通讯作者：
Park, Ji-Ho
中科院分区：
文献类型：
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作者：
Kim, Jiyoung;Santos, Olavo Amorim;Park, Ji-Ho
光敏剂（ps）的亚细胞定位决定了光动力治疗的疗效。然而，在亚细胞区室中，很少有人将PSs选择性地递送到质膜中，并研究膜定位PSs的光疗效果。在这里，我们开发了一种脂质体递送系统，将疏水性ps选择性地定位到质膜上。制备了膜融合脂质体（MFLs），其膜与质膜融合，用于PSs的膜定位。负载znpc的MFLs处理的细胞光疗效果优于负载znpc的非促梭性脂质体处理的细胞，后者是一种传统的脂质体配方，通过内吞作用将ps递送到细胞内腔室。ZnPc分子的膜定位导致辐照后膜的快速破坏和随后的坏死样细胞死亡。在负载znpc的MFLs处理的细胞中，活性氧的膜定位产生可能是有效破坏质膜的原因。因此，本工作提供了一种新的传递方法，可以选择性地将ps定位到质膜中，并增强光疗效果。(C) 2014 Elsevier B.V.版权所有
Subcellular localization of photosensitizers (PSs) determines the therapeutic efficacy in the photodynamic therapy. However, among the subcellular compartments, there has been little effort to deliver the PSs selectively into the plasma membrane and examine the phototherapeutic efficacy of membrane-localized PSs. Here, we developed a liposomal delivery system to localize the hydrophobic PSs selectively into the plasma membrane. The membrane fusogenic liposomes (MFLs), the membrane of which is engineered to fuse with the plasma membrane, was prepared for the membrane localization of PSs. The phototherapeutic efficacy of cells treated with ZnPc-loaded MFLs was superior over that of cells treated with ZnPc-loaded non-fusogenic liposomes, which is the conventional liposomal formulation that delivers the PSs into the intracellular compartments via endocytosis. The membrane localization of ZnPc molecules led to rapid membrane disruption upon irradiation and subsequent necrosis-like cell death. The membrane-localized generation of reactive oxygen species in the cells treated with ZnPc-loaded MFLs was likely to account for the effective disruption of plasma membrane. Thus, this work provides a novel delivery method to localize the PSs selectively into the plasma membrane with the enhanced phototherapeutic efficacy. (C) 2014 Elsevier B.V. All rights reserved.