摘要
将疏水性光敏剂原卟啉(PpIX)和亲水性多肽结合,设计并合成一种刺激响应型两亲性嵌合肽PpIX-GGK(TPP)G-GFLGR8 GD(PTGR),利用该多肽在水溶液中能发生自组装行为,从而得到前药胶束。该胶束在RGD肽的作用下能有效富集在表面过度表达整合素αvβ3的肿瘤细胞周围;在R8穿膜肽的帮助下快速进入肿瘤细胞内;由于癌细胞细胞质内存在大量的组织蛋白酶B,其能够有效破坏GFLG多肽片段,导致前药胶束结构瓦解并释放出疏水性PpIX衍生物。此外,在三苯基膦(TPP)的引导下,组织蛋白酶B光敏剂原卟啉(PpIX)能高效富集在线粒体周围,并在特定光照条件下产生大量的活性氧(ROS),从而有效破坏线粒体,进而诱导细胞凋亡和坏死,实现光动力治疗(PDT)肿瘤的目的。这种将光敏剂运输到亚细胞部位的策略,为光动力治疗的高效发挥开辟了一条新的途径。
A cathepsin B-sensitive amphiphilic chimeric peptide PpIX-GGK(TPP)G-GFLGR8 GD(PTGR)was developed for photodynamic therapy(PDT).The chimeric peptide composed of the hydrophobic photosensitizer protoporphyrin(PpIX)and the hydrophilic peptide could be self-assembled into prodrug micelles in the water.Due to the presence of RGD,the prodrug micelles would recognize the tumor cells with integrinαvβ3 over-expression,and then entered into tumor cells quickly with the help of cell-penetrating peptides(CPP)R8.Once exposed to tumor cytoplasm,the oligopeptide linker(GFLG)between the CPP and the hydrophobic PpIX would be hydrolyzed by the over-expressed cathepsin B enzyme,resulting in the controlled release of PpIX in cytoplasm.Meanwhile,the PpIX would efficiently enrich in the cell mitochondria under the guidance of triphenylphosphine(TPP),and generated the reactive oxygen species(ROS)with light irradiation.Due to the photo-toxicity of ROS,PpIX-GGK(TPP)G-GFLGR8 GD(PTGR)significantly disrupted mitochondria membrane,inducing tumor cells apoptosis and necrosis.What's more,this strategy of transporting photosensitizers to subcellular sites via prodrug micelles opened up a new avenue for photodynamic therapy(PDT).
作者
田翔
程崟家
张爱清
TIAN Xiang;CHENGYinjia;ZHANG Aiqing(School of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, China)
出处
《功能材料》
EI
CAS
CSCD
北大核心
2020年第4期4084-4089,4095,共7页
Journal of Functional Materials
基金
国家自然科学青年基金资助项目(51703251)。
关键词
光动力治疗
光敏剂
多肽
线粒体
photodynamic therapy
photosensitizer
peptide
mitochondria
