| Title |
iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice
|
|---|---|
| Published in |
Tumor Biology, February 2016
|
| DOI | 10.1007/s13277-016-4961-x |
| Pubmed ID | |
| Authors |
Wang Qifan, Ning Fen, Xue Ying, Feng Xinwei, Du Jun, Zhang Ge |
| 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 22% |
| Researcher | 3 | 13% |
| Student > Master | 3 | 13% |
| Student > Bachelor | 2 | 9% |
| Student > Postgraduate | 2 | 9% |
| Other | 3 | 13% |
| Unknown | 5 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 4 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Medicine and Dentistry | 3 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 9% |
| Arts and Humanities | 1 | 4% |
| Other | 3 | 13% |
| Unknown | 7 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2016.
All research outputs
#20,306,690
of 22,846,662 outputs
Outputs from Tumor Biology
#1,834
of 2,622 outputs
Outputs of similar age
#337,062
of 400,575 outputs
Outputs of similar age from Tumor Biology
#122
of 182 outputs
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