A Tumor Targeted Chimeric Peptide for Synergistic Endosomal Escape and Therapy by Dual‐Stage Light Manipulation. (13th January 2015)

• Record Type: Journal Article
• Authors: Han, Kai; Lei, Qi; Jia, Hui‐Zhen; Wang, Shi‐Bo; Yin, Wei‐Na; Chen, Wei‐Hai; Cheng, Si‐Xue; Zhang, Xian‐Zheng
• Is Part Of: Advanced functional materials. Volume 25:Number 8(2015)
• Page Start: 1248
• Page End: 1257
• Publication Date: 2015-01-13
• Subjects: chimeric peptide -- endosomal escape -- photochemical internalization -- photodynamic therapy; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201403190
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract : In this study, a pH sensitive chimeric peptide is developed to codeliver a photosensitizer, protoporphyrin IX (PpIX), and plasmid DNA simultaneously. In the presence of matrix metalloproteinase‐2 (MMP‐2), the chimeric peptide undergoes the process of hydrolysis of PLGVR peptide sequence, exfoliation of PEG, and increase of positive charges. As a result, the chimeric peptide can be preferentially uptaken by MMP‐2 rich tumor cells. To realize synergistic effect of drug and gene delivery, a dual‐stage light irradiation strategy is developed, i.e., the short time light irradiation can efficiently enhance the endosomal escape of the chimeric peptide/PpIX/DNA complexes by the formation the reactive oxygen species (ROS), resulting in synergistic endosomal escape and improved DNA expression. In addition, due to the screened phototoxicity of PpIX, short time light irradiation does not lead to detectable changes in the cell viability. After the gene transfection, the screened phototoxicity of PpIX is subsequently stimulated by long time irradiation to achieve high synergistic efficacy of photodynamic and gene therapies. Both in vitro and in vivo studies confirm the chimeric peptide‐based nanocarrier with a good synergistic effect is a promising nanoplatform for tumor treatments. Abstract : A MMP‐2 responsiveness chimeric peptide is reported to transport the photosensitizer PpIX and DNA to the target cells. Importantly, a dual‐stage light irradiation strategy is used to enhance the endosome escape via photochemical internalization. A high therapeutic index is achieved due to the synergistic effect between gene therapy and photodynamic therapy.