title: Protease-Activable Cell-Penetrating Peptide-Protoporphyrin Conjugate for Targeted Photodynamic Therapy in Vivo.
abstract: In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R9GPLGLAGE8, ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R9) would be blocked by a polyanionic peptide (E8) through intramolecular electrostatic attraction. Once exposed to MMP-2 existing at the tumor site, proteolysis of the oligopeptide linker (GPLGLAG) between the CPP and the polyanionic peptide would dissociate the inhibitory polyanions and release CPP-PpIX for photodynamic therapy (PDT). It was found that after tail vein injection the ACPP-PpIX conjugate could accumulate effectively at the tumor site with the fluorescence enhancement which was beneficial for tumor diagnosis and image-guided PDT. After further administration with irradiation, both the solid tumor size and weight had a significant suppression (reduced by more than 90%) with a low systemic toxicity. This ACPP-PpIX conjugate delivery system activated by MMP-2 would be a promising strategy for tumor-targeted treatment.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Wen-Xiu
authors.initials: WX
authors.lastname: Qiu
authors.forename: Li-Han
authors.initials: LH
authors.lastname: Liu
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Bo-Ru
authors.initials: BR
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Hubei Provincial Cooperative Innovation Center of Industrial Fermentation , Wuhan 430068, PR China.
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010778:Photochemotherapy; D011524:Protoporphyrins / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D011524:Protoporphyrins; D020778:Matrix Metalloproteinase 2
keywords: cell-penetrating peptide; matrix metalloproteinases-2; photodynamic therapy; theranostic; tumor targeting