A Cytotoxic Peptide-Drug Conjugate for Tumor-Specific Delivery of Co-Injected Molecules

Authors

Norio Miyamura
Chisato M Yamazaki
Yasuaki Anami
Kyoji Tsuchikama
Kazuki N Sugahara

Language

English

Publication Date

1-1-2025

Journal

PLoS One

DOI

10.1371/journal.pone.0331564

PMID

40892758

PMCID

PMC12404482

PubMedCentral® Posted Date

9-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively to tumors in mice, and extensively spread in the extravascular tumor tissue in line with the tumor-penetrating capacity of iRGD. iRGD-MMAF also significantly enhanced tumor-specific entry of a co-injected molecule by serving as an effective drug delivery scaffold. The results indicate that a chemically modified iRGD peptide with an added therapeutic benefit retains its ability to deliver co-injected agents to tumors.

Keywords

Animals, Mice, Oligopeptides, Humans, Drug Delivery Systems, Cell Line, Tumor, Antineoplastic Agents, Neoplasms

Published Open-Access

yes

Recommended Citation

Miyamura, Norio; Yamazaki, Chisato M; Anami, Yasuaki; et al., "A Cytotoxic Peptide-Drug Conjugate for Tumor-Specific Delivery of Co-Injected Molecules" (2025). Faculty, Staff and Student Publications. 6607.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6607