Department of Pharmaceutical Sciences and Guangdong Key Laboratory of New Drug Screening Southern Medical University, Guangzhou, 510515, P. R. China.
College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing, 210037, P. R. China.
Adv Healthc Mater. 2020 Jan;9(1):e1901100. doi: 10.1002/adhm.201901100. Epub 2019 Nov 25.
Nowadays, cell membrane-targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane-targeted self-delivery theranostic chimeric peptide CMP-PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real-time therapeutic feedback. Self-assembled CMP-PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP-PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)-carboxyfluorescein (FAM) and 4-(dimethylaminoazo)-benzene-4-carboxylic acid (Dabcyl). More importantly, CMP-PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP-PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp-Glu-Val-Asp (DEVD) is subsequently cleaved by activated caspase-3 and activated caspase-7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase-3 in vitro and in vivo to feedback real-time PDT therapeutic efficacy. In general, a novel cell membrane-targeted self-delivery theranostic chimeric peptide offers new promise for effective imaging-guided PDT.
现如今，细胞膜靶向治疗因其能够避免细胞屏障而具有高效的抗肿瘤效果，受到了广泛关注。在这里，设计了一种细胞膜靶向自传递治疗性嵌合肽 CMP-PpIX，用于同时靶向肿瘤的光动力治疗（PDT）和实时治疗反馈。自组装的 CMP-PpIX 纳米颗粒可以通过增强的通透性和保留效应有效地在肿瘤中积累，而无需额外的载体。并且，这种嵌合肽 CMP-PpIX 具有低背景荧光，这是由于其在 5(6)-羧基荧光素（FAM）和 4-（二甲基氨基偶氮）-苯-4-羧酸（Dabcyl）之间具有相对较高的分子内Förster 共振能量转移（FRET）猝灭效率。更重要的是，CMP-PpIX 可以锚定在肿瘤细胞膜上超过 8 小时。在照射下，CMP-PpIX 产生的活性氧直接损伤细胞膜并迅速诱导细胞凋亡，这显著提高了 PDT 在体外和体内的疗效。然后，被激活的 caspase-3 和 caspase-7 相继切割肽序列天冬氨酸-谷氨酸-缬氨酸-天冬氨酸（DEVD），从而分离 FAM 和 Dabcyl 并终止 FRET 过程。因此，FAM 的荧光恢复以监测体外和体内激活的 caspase-3 的表达，从而反馈实时 PDT 治疗效果。总的来说，一种新型的细胞膜靶向自传递治疗性嵌合肽为有效的成像引导 PDT 提供了新的希望。
