Self-quenching polysaccharide-based nanogels of pullulan/folate-photosensitizer conjugates for photodynamic therapy
Self-quenching polysaccharide-based nanogels of pullulan/folate-photosensitizer conjugates for photodynamic therapy
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DOI：
10.1016/j.biomaterials.2010.04.030
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发表时间：
2010-08-01
期刊：
影响因子：
14
通讯作者：
Na, Kun
中科院分区：
文献类型：
--
作者：
Bae, Byoung-chan;Na, Kun
研究了由普鲁兰多糖/叶酸-脱镁叶绿酸-a（Pheo-A）缀合物合成的基于自猝灭多糖的纳米凝胶在降低光敏剂（PS）在正常组织中的光毒性和增强肿瘤治疗功效方面的潜力。虽然纳米凝胶在有机溶剂（DMF）中显示出包括荧光和单线态氧产生的光活性性质，但由于光敏剂部分的自猝灭（类似于荧光共振能量转移（FRET）效应），这些性质在PBS中被抑制。当PFP 2纳米凝胶与酯酶或HeLa癌细胞共孵育时，其光活性恢复。这些结果表明，纳米凝胶通过叶酸受体介导的内吞作用内化在癌细胞中，然后被溶酶体中的各种酶分解，导致光活性的恢复。在体内研究中，游离Pheo-A在注射后立即显示荧光;然而，在注射后30分钟检测到纳米凝胶荧光，在12小时内显著增加，并维持超过3周。纳米凝胶的光毒性性质与游离Pheo-A的光毒性性质相似，导致IC 50 < 0.25和细胞毒性细胞死亡。基于这些结果，我们认为自猝灭PFP纳米凝胶可用于设计具有最小不利光毒性的新的光动力疗法。(C)2010爱思唯尔有限公司保留所有权利。
Self-quenching polysaccharide-based nanogels synthesized from pullulan/folate-pheophorbide-a (Pheo-A) conjugates were investigated for their potential to reduce photosensitizer (PS) phototoxicity in normal tissue and to enhance the efficacy of tumor treatment. While the nanogels showed photoactive properties including fluorescence and singlet oxygen generation in organic solvent (DMF), these properties were suppressed in PBS due to the self-quenching of photosensitizer moieties similar to the fluorescence resonance energy transfer (FRET) effect. When the PFP2 nanogel was co-incubated with esterase or HeLa cancer cells, its photoactivity was restored. These results demonstrate that the nanogel was internalized in cancer cells by folate receptor-mediated endocytosis and was then disintegrated by various enzymes in the lysosome, leading to restoration of photoactivity. In an in vivo study, free Pheo-A showed fluorescence immediately after injection; however, nanogel fluorescence was detected 30 min after injection, increased significantly over 12 h, and was maintained beyond 3 weeks. The phototoxic properties of the nanogel were similar to those of free Pheo-A, resulting in an IC50 < 0.25 and apoptic cell death. Based on these results, we suggest that self-quenching PFP nanogels can be used to design new photodynamic therapies with minimal unfavorable phototoxicity. (C) 2010 Elsevier Ltd. All rights reserved.