PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects
PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects
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DOI：
10.1039/c5pp00274e
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Lassalle, Henri-Pierre
中科院分区：
文献类型：
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作者：
Bastien, Estelle;Schneider, Raphael;Lassalle, Henri-Pierre
目前，人们对开发用于全身光动力治疗的高效且特定的载体递送平台产生了极大的兴趣。因此，我们的目标是开发光敏剂二氢卟酚 e6 (Ce6) 和 PAMAM G4.5 树枝状聚合物之间的共价缀合物。单线态氧生成 (SOG) 效率和荧光发射受到 Ce6 与树枝状聚合物共价结合的适度影响。与游离 Ce6 相比，PAMAM 锚定的 Ce6 显示出更高的光动力效应，这归因于在肿瘤细胞模型中更好的内化。使用特定的抑制条件和共焦荧光显微镜研究了我们不同化合物的细胞内命运和内化途径。游离的 Ce6 通过简单的扩散机制进入细胞，而 G4.5-Ce6-PEG 内化依赖于小凹途径，而 G4.5-Ce6 则受到网格蛋白介导的内吞途径的影响。 PAMAM 锚定的 Ce6（无论是否聚乙二醇化）的亚细胞定位非常相似，表明纳米颗粒在细胞中的行为相似。总之，我们已经证明，聚乙二醇化 G4.5 PAMAM-Ce6 树枝状聚合物可以提供有效的生物相容性纳米粒子，以改善临床前肿瘤模型中的光动力治疗。
There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic photodynamic therapy. Therefore, we aimed to develop covalent conjugates between the photosensitizer chlorin e6 (Ce6) and PAMAM G4.5 dendrimers. Singlet oxygen generation (SOG) efficiency and fluorescence emission were moderately affected by the covalent binding of the Ce6 to the dendrimer. Compared to free Ce6, PAMAM anchored Ce6 displays a much higher photodynamic effect, which is ascribable to better internalization in a tumor cell model. Intracellular fate and internalization pathway of our different compounds were investigated using specific inhibition conditions and confocal fluorescence microscopy. Free Ce6 was shown to enter the cells by a simple diffusion mechanism, while G4.5-Ce6-PEG internalization was dependent on the caveolae pathway, whereas G4.5-Ce6 was subjected to the clathrin-mediated endocytosis pathway. Subcellular localization of PAMAM anchored Ce6, PEGylated or not, was very similar suggesting that the nanoparticles behave similarly in the cells. As a conclusion, we have demonstrated that PEGylated G4.5 PAMAM-Ce6 dendrimers may offer effective biocompatible nanoparticles for improved photodynamic treatment in a preclinical tumor model.