{"doi":"10.1126/sciadv.adf6854","title":"Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy","abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) can reinvigorate T cells to eradicate tumor cells, showing great potential in combating various types of tumors. We propose a delivery strategy to enhance tumor-selective ICI accumulation, which leverages the responsiveness of platelets and platelet-derivatives to coagulation cascade signals. A fused protein tTF-RGD targets tumor angiogenic blood vessel endothelial cells and initiates the coagulation locoregionally at the tumor site, forming a “cellular hive” to recruit anti–PD-1 antibody (aPD-1)–conjugated platelets to the tumor site and subsequently activating platelets to release aPD-1 antibody to reactivate T cells for improved immunotherapy. Moreover, on a patient-derived xenograft breast cancer model, the platelet membrane–coated nanoparticles can also respond to the coagulation signals initiated by tTF-RGD, thus enhancing the accumulation and antitumor efficacy of the loaded chemotherapeutics. Our study illustrates a versatile platform technology to enhance the local accumulation of ICIs and chemodrugs by taking advantage of the responsiveness of platelets and platelet derivatives to thrombosis.</jats:p>","journal":"Science Advances","year":2023,"id":635866,"datarank":0.5775221402565088,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"self_citation_contribution":0.5775221402565088,"citation_network_contribution":0.0,"self_endowment_contribution":0.5775221402565088,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"citer_count":0,"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":452734,"name":"Wen Li","orcid":"0000-0002-7538-5422","position":1,"is_corresponding":false},{"id":898641,"name":"Zhaoting Li","orcid":"0000-0002-4596-9603","position":2,"is_corresponding":false},{"id":1649936,"name":"Fanyi Mo","orcid":null,"position":3,"is_corresponding":false},{"id":905059,"name":"Yu Chen","orcid":"0000-0002-2266-994X","position":4,"is_corresponding":false},{"id":301096,"name":"Mari Iida","orcid":"0000-0001-7168-8680","position":5,"is_corresponding":false},{"id":301097,"name":"Deric L. Wheeler","orcid":"0000-0001-5915-3675","position":6,"is_corresponding":false},{"id":434470,"name":"Quanyin Hu","orcid":"0000-0003-2946-1655","position":7,"is_corresponding":false},{"id":841223,"name":"Yixin Wang","orcid":"0000-0002-6394-0214","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Active recruitment of anti–PD-1–conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy","abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) can reinvigorate T cells to eradicate tumor cells, showing great potential in combating various types of tumors. We propose a delivery strategy to enhance tumor-selective ICI accumulation, which leverages the responsiveness of platelets and platelet-derivatives to coagulation cascade signals. A fused protein tTF-RGD targets tumor angiogenic blood vessel endothelial cells and initiates the coagulation locoregionally at the tumor site, forming a “cellular hive” to recruit anti–PD-1 antibody (aPD-1)–conjugated platelets to the tumor site and subsequently activating platelets to release aPD-1 antibody to reactivate T cells for improved immunotherapy. Moreover, on a patient-derived xenograft breast cancer model, the platelet membrane–coated nanoparticles can also respond to the coagulation signals initiated by tTF-RGD, thus enhancing the accumulation and antitumor efficacy of the loaded chemotherapeutics. Our study illustrates a versatile platform technology to enhance the local accumulation of ICIs and chemodrugs by taking advantage of the responsiveness of platelets and platelet derivatives to thrombosis.</jats:p>","is_dataset_classified":null,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36989364","pmcid":"PMC10058243","openalex_id":"https://openalex.org/W4361302170","authors":[],"funders":[],"total_grants":0,"fwci":5.3117,"citation_percentile":0.96957886,"influential_citations":0,"citation_trend":[{"year":2023,"count":6},{"year":2024,"count":23},{"year":2025,"count":9},{"year":2026,"count":8}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.adf6854?download=true","host_type":"journal"},{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.adf6854?download=true","host_type":"publisher"},{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.adf6854","host_type":"publisher"},{"url":"https://doi.org/10.1126/sciadv.adf6854","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36989364","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10058243","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10058243/pdf/sciadv.adf6854.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10058243","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10058243?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","Immunotherapy and Immune Responses","Immune Cell Function and Interaction"],"mesh_terms":["Animals","Disease Models, Animal","Humans","Immunotherapy","Neoplasms","Oligopeptides","Thrombosis","Endothelial Cells","Programmed Cell Death 1 Receptor"],"keywords":["Platelet","Immunotherapy","Cancer research","Coagulation","Platelet activation","Medicine","Immune system","Tumor microenvironment","Cancer immunotherapy","Thrombosis","Pharmacology","Immunology","Chemistry","Tumor cells","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"uniprot"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T15:43:32.625178Z","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":[]}