{"doi":"10.2147/dddt.s562135","title":"Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles","abstract":null,"journal":"Drug Design, Development and Therapy","year":2026,"id":642656,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353474,"name":"Thuy Do","orcid":"0000-0002-5668-2181","position":1,"is_corresponding":false},{"id":1671742,"name":"Clare Dinh","orcid":null,"position":2,"is_corresponding":false},{"id":1671743,"name":"Dorna Davani-Davari","orcid":null,"position":3,"is_corresponding":false},{"id":1671744,"name":"Max Foroughi","orcid":null,"position":4,"is_corresponding":false},{"id":1671745,"name":"Troy Khong","orcid":null,"position":5,"is_corresponding":false},{"id":1671746,"name":"Mahsa Moazen","orcid":null,"position":6,"is_corresponding":false},{"id":1376691,"name":"Amir Nasrolahi Shirazi","orcid":null,"position":7,"is_corresponding":false},{"id":409999,"name":"Keykavous Parang","orcid":"0000-0001-8600-0893","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles","abstract":"Abstract: Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss key design elements (targeting peptides, cleavable/non-cleavable linkers, and payloads) and how these drive mechanisms of tumor delivery and intracellular drug release. Mechanistically, PDCs bind receptors or translocate across membranes, undergo endocytosis, and exploit stimuli-responsive linkers or cell-penetrating peptides to release drugs. Many PDCs can self-assemble into nanoscale structures in aqueous environments. We illustrate PDC concepts through specific instances, such as the brain-penetrant paclitaxel trevatide (ANG1005, paclitaxel-Angiopep-2), the radiotherapeutic lutetium ( 177 Lu)-DOTATATE (Lutathera), and the LyP-1-conjugated doxorubicin-loaded liposomes (LyP-1-doxorubicin conjugate) for triple-negative breast cancer. Persistent challenges include in vivo stability (premature drug release and metabolic clearance), tumor heterogeneity (variable receptor expression), and manufacturing scale-up. We also address regulatory hurdles that have limited PDC clinical success; for example, currently, only lutetium ( 177 Lu)-DOTATATE is FDA-approved (others, like melphalan flufenamide (melflufen), have faced setbacks). Finally, we outline future directions, including theranostic PDCs, AI-assisted peptide optimization, dual-stimuli linkers, and integration with nanomaterials, to further enhance targeting and efficacy. This comprehensive review integrates findings from recent literature and provides an in-depth perspective on the design, advantages, limitations, and future prospects of PDCs in cancer therapy. Keywords: antibody-drug conjugate, cancer, drug delivery, linker chemistry, nanotechnology, peptide-drug conjugate, targeting peptide, theranostics, tumor penetration","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41710577","pmcid":null,"openalex_id":"https://openalex.org/W7128685907","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R15 CA301437","title":null}],"total_grants":1,"fwci":22.0895,"citation_percentile":0.99543001,"influential_citations":0,"citation_trend":[{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.2147/dddt.s562135","host_type":"journal"},{"url":"https://doi.org/10.2147/dddt.s562135","host_type":"publisher"},{"url":"https://www.dovepress.com/article/download/111978","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41710577","host_type":"repository"},{"url":"https://digitalcommons.chapman.edu/pharmacy_articles/1209","host_type":"repository"},{"url":"https://www.dovepress.com/tumor-targeting-with-peptide-drug-conjugates-showcasing-key-progress-a-peer-reviewed-fulltext-article-DDDT","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12912028/","host_type":"repository"}],"fields_of_study":["RNA Interference and Gene Delivery","Nanoparticle-Based Drug Delivery","Supramolecular Self-Assembly in Materials","Humans","Antineoplastic Agents","Neoplasms","Drug Delivery Systems","Peptides","Animals"],"mesh_terms":["Animals","Antineoplastic Agents","Humans","Neoplasms","Peptides","Drug Delivery Systems"],"keywords":["Paclitaxel","Drug delivery","Drug","Nanocarriers","Homing (biology)","Targeted drug delivery","antibody-drug conjugate","cancer","linker chemistry","nanotechnology","peptide-drug conjugate","targeting peptide","theranostics","tumor penetration"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T01:59:27.315603Z","pmid":null,"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":[]}