{"doi":"10.1371/journal.pone.0331564","title":"A cytotoxic peptide-drug conjugate for tumor-specific delivery of co-injected molecules","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.","journal":"PLoS ONE","year":2025,"id":573981,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1198766,"name":"Chisato M. Yamazaki","orcid":"0000-0002-0785-7352","position":1,"is_corresponding":false},{"id":833161,"name":"Yasuaki Anami","orcid":"0000-0001-5136-7708","position":2,"is_corresponding":false},{"id":833165,"name":"Kyoji Tsuchikama","orcid":"0000-0002-2359-0408","position":3,"is_corresponding":false},{"id":642062,"name":"Kazuki N. Sugahara","orcid":"0000-0002-4946-192X","position":4,"is_corresponding":false},{"id":642061,"name":"Norio Miyamura","orcid":"0000-0003-2251-3408","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40892758","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}