State Key Laboratory of Biochemical Engineering Institute of Process Engineering, Chinese Academy of Sciences No.1 North second Street, Zhongguancun , 100190 Beijing , China.
Future Industries Institute University of South Australia Mawson Lakes , South Australia 5095 , Australia.
ACS Appl Mater Interfaces. 2018 Aug 29;10(34):28420-28427. doi: 10.1021/acsami.8b09933. Epub 2018 Aug 15.
Employing nanoscaled materials as photosensitizer (PS) carriers is an effective strategy to solve the problem of poor solubility and low tumor selectivity of hydrophobic PS in photodynamic therapy (PDT), which compulsorily requires the PS release in PDT implementation. However, the complicated environment in vivo makes it difficult to precisely design and control the release process and the delivery process requires real-time tracking. Developing a delivery strategy of hydrophobic PS in the monomeric form with fluorescent emission and without consideration of the PS release in the PDT process, is in urgent demand. Herein, we report a versatile and potent strategy for fabrication of photodynamic nanoparticles (nanoPSs) with featuring the monomeric PS based on aromatic peptide-modulated self-assembly of porphyrin derivatives. Aromatic peptides within nanoPSs can isolate hydrophobic porphyrins from each other, resulting in monomeric porphyrin delivery with real-time fluorescence tracking property and avoiding self-aggregation and hence porphyrin release. Moreover, partially charged porphyrins tend to expose on the surface of nanoPSs, facilitating production and diffusion of O. The highest O yield can be achieved with porphyrin loading as low as 6 wt %, reducing side effects of excessive porphyrin injection. The nanoPSs show enhanced PDT efficacy in vitro and in vivo leading to complete tumor eradication. This study highlights opportunities for development of active photodynamic nanoparticles and provides an alternative strategy for delivery of hydrophobic photosensitive drugs with enhanced therapeutic effects.
将纳米材料用作光敏剂 (PS) 载体是解决疏水性 PS 在光动力疗法 (PDT) 中溶解度差和肿瘤选择性低的问题的有效策略，这在 PDT 实施中强制要求 PS 释放。然而，体内复杂的环境使得难以精确设计和控制释放过程，并且输送过程需要实时跟踪。因此，迫切需要开发一种以单体形式输送疏水性 PS 的输送策略，该策略具有荧光发射且不考虑 PDT 过程中的 PS 释放。在此，我们报告了一种基于芳香肽调节卟啉衍生物自组装的多功能、高效制备光动力纳米粒子 (nanoPSs) 的策略，该策略的特征在于基于单体 PS。纳米 PSs 内的芳香肽可以将疏水性卟啉彼此隔开，从而实现单体卟啉的输送，并具有实时荧光跟踪特性，避免自聚集和卟啉释放。此外，部分带电的卟啉倾向于暴露在纳米 PSs 的表面上，有利于 O 的产生和扩散。以低至 6wt%的卟啉负载量即可实现最高的 O 产量，从而减少了过量卟啉注射的副作用。纳米 PSs 在体外和体内均显示出增强的 PDT 效果，导致完全消除肿瘤。这项研究突出了开发主动光动力纳米粒子的机会，并为增强治疗效果的疏水性光敏药物的输送提供了替代策略。
