State Key Laboratory of Structural Chemistry and CAS Key Laboratory of Design and Assembly of Functional Nanostructures , Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences , Fuzhou , Fujian 350002 , P. R. China.
College of Life Science , Fujian Agriculture and Forestry University , Fuzhou , Fujian 350002 , P. R. China.
ACS Appl Mater Interfaces. 2018 May 9;10(18):15369-15380. doi: 10.1021/acsami.7b19058. Epub 2018 Apr 24.
Clinical photosensitizers suffer from the disadvantages of fast photobleaching and high systemic toxicities because of the off-target photodynamic effects. To address these problems, we report a self-assembled pentalysine-phthalocyanine assembly nanodots (PPAN) fabricated by an amphipathic photosensitizer-peptide conjugate. We triggered the photodynamic therapy effects of photosensitizers by precisely controlling the assembly and disintegration of the nanodots. In physiological aqueous conditions, PPAN exhibited a size-tunable spherical conformation with a highly positive shell of the polypeptides and a hydrophobic core of the π-stacking Pc moieties. The assembly conformation suppressed the fluorescence and the reactive oxygen species generation of the monomeric photosensitizer molecules (mono-Pc) and thus declined the photobleaching and off-target photodynamic effects. However, tumor cells disintegrated PPAN and released the mono-Pc molecules, which exhibited fluorescence for detection and the photodynamic effects for the elimination of the tumor tissues. The molecular dynamics simulations revealed the various assembly configurations of PPAN and illustrated the assembly mechanism. At the cellular level, PPAN exhibited a remarkable phototoxicity to breast cancer cells with the IC values in a low nanomolar range. By using the subcutaneous and orthotopic breast cancer animal models, we also demonstrated the excellent antitumor efficacies of PPAN in vivo.
临床光动力治疗剂由于其非靶向光动力效应而存在快速光漂白和高全身毒性等缺点。为了解决这些问题，我们报告了一种由两亲性光敏剂-肽缀合物制备的自组装五赖氨酸-酞菁组装纳米点（PPAN）。我们通过精确控制纳米点的组装和分解来触发光动力治疗剂的光动力治疗效果。在生理水相条件下，PPAN 呈现出尺寸可调的球形构象，具有高度正电的多肽外壳和π-堆积 Pc 部分的疏水性核心。组装构象抑制了单体光敏剂分子（单体-Pc）的荧光和活性氧生成，从而降低了光漂白和非靶向光动力效应。然而，肿瘤细胞会使 PPAN 解体并释放出单体-Pc 分子，这些分子会发出荧光以供检测，并具有光动力效应来消除肿瘤组织。分子动力学模拟揭示了 PPAN 的各种组装构型，并说明了其组装机制。在细胞水平上，PPAN 对乳腺癌细胞表现出显著的光毒性，IC 值处于低纳摩尔范围。通过使用皮下和原位乳腺癌动物模型，我们还在体内证明了 PPAN 的优异抗肿瘤疗效。
