NDLI: IRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice

Content Provider	Springer Nature Link
Author	Qifan, Wang Fen, Ning Ying, Xue Xinwei, Feng Jun, Du Ge, Zhang
Copyright Year	2016
Abstract	The use of cytolytic peptides with potential therapeutic properties is a promising approach to cancer therapy due to their convenient automated synthesis and their capacity for modifications. However, the use of cytolytic peptides is limited due to their nonspecific cytolytic activity. In this study, we designed a tumor-targeting proapoptotic system based on an amphipathic D-amino acid-modified apoptotic peptide, KLA, a variant of (KLAKLAK)$_{2}$, which is fused with a linear tumor-penetrating homing peptide iRGD through specific cathepsin B (CTSB) cleavage sequences that are overexpressed in many types of tumor tissues. Our data show that the procytotoxic peptide $_{D}$(KLAKLAKKLAKLA)K-GG-iRGD (m(KLA)-iRGD) is internalized into cultured tumor cells through a neuropilin-1 (NRP1)-activated pathway by iRGD delivery. Once inside the cells, the peptide triggers rapid apoptosis through both the mitochondrial-induced apoptotic pathway and the death receptor pathway in NRP1+/αvβ3/CTSB+ tumor cells. Furthermore, m(KLA)-iRGD spread extensively within the tumor tissue when it was injected into 4T1 tumor-bearing mice. The m(KLA)-iRGD peptide inhibited tumor growth to a certain degree, resulting in a significant reduction in tumor volume (P < 0.05) and the total inhibition of metastasis at the end of the treatment. These results suggest that m(KLA)-iRGD has the potential for development as a new antitumor drug.
Starting Page	10643
Ending Page	10652
Page Count	10
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	8
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-02-11
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	iRGD Cathepsin B Tumor growth Metastasis Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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