Protease-Activable Cell-Penetrating Peptide-Protoporphyrin Conjugate for Targeted Photodynamic Therapy in Vivo

被引：77

作者：

Li, Shi-Ying ^{[1
,2
]}

Cheng, Hong ^{[1
,2
]}

Qiu, Wen-Xiu ^{[1
,2
]}

Liu, Li-Han ^{[1
,2
]}

Chen, Si ^{[1
,2
]}

Hu, Ying ^{[1
,2
]}

Xie, Bo-Ru ^{[1
,2
]}

Li, Bin ^{[1
,2
]}

Zhang, Xian-Zheng ^{[1
,2
,3
,4
]}

机构：

[1] Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China

[2] Wuhan Univ, Dept Chem, Wuhan 430072, Peoples R China

[3] Wuhan Univ, Inst Adv Studies, Wuhan 430072, Peoples R China

[4] Hubei Prov Cooperat Innovat Ctr Ind Fermentat, Wuhan 430068, Peoples R China

来源：

ACS APPLIED MATERIALS & INTERFACES | 2015年 / 7卷 / 51期

基金：

中国国家自然科学基金;

关键词：

cell-penetrating peptide; photodynamic therapy; tumor targeting; theranostic; matrix metalloproteinases-2; DRUG-DELIVERY; INTRACELLULAR DELIVERY; CANCER-THERAPY; ACTIVATION; APOPTOSIS; PROTEINS; PRODRUG; TUMORS; CARGO; PROBE;

D O I：

10.1021/acsami.5b08637

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R(9)GPLGLAGE(8), ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R-9) would be blocked by a polyanionic peptide (E-8) 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.

引用

页码：28319 / 28329

页数：11

共 43 条

[1] Inhibition of Cancer Cell Proliferation and Breast Tumor Targeting of pHLIP-Monomethyl Auristatin E Conjugates [J].