{"doi":"10.1016/j.celbio.2025.100221","title":"Cerenkov radiation modulates the extracellular matrix for improved pancreatic cancer chemotherapy","abstract":"Abundant cancer-associated fibroblasts (CAFs) in pancreatic tumors cause robust interstitial fibrosis and abnormal vascular structure, hindering the delivery and effectiveness of small-molecule therapeutics, leading to poor clinical outcomes. We developed a strategy to modulate the extracellular matrix (ECM) in pancreatic cancer to enhance chemotherapy through sequential administration of TiO 2 nanoparticles (NPs), [ 68 Ga]Ga-FAPI-04 ([ 68 Ga]Ga-FAPI), and the chemotherapeutic drug tirapazamine (TPZ). The positron emission tomography tracer [ 68 Ga]Ga-FAPI specifically targets CAFs and serves as an internal excitation source for Cerenkov radiation-mediated photodynamic therapy (CR-PDT). TiO 2 NPs generate cytotoxic reactive oxygen species upon CR, destroying tumor cells and CAFs. As a result, CR-PDT reduces the dense stromal barrier by inhibiting the formation and secretion of fibrous collagen, improving the delivery of TPZ. Additionally, CR-PDT consumes oxygen throughout the process, intensifying tumor hypoxia, which further activates TPZ, a hypoxia-activated and bio-reductive prodrug. Our design of CR-PDT-mediated ECM modulation brings new ideas for the exploration and application of radiotracer-combined nanomedicine in cancer therapy, particularly for cancers with abundant ECM.","journal":"Cell Biomaterials","year":2025,"id":576886,"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":0.9614,"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":1485694,"name":"Han Wang","orcid":"0000-0003-0824-2912","position":1,"is_corresponding":false},{"id":322941,"name":"Shuai Zhao","orcid":"0009-0007-0006-8987","position":2,"is_corresponding":false},{"id":1485695,"name":"Tao Wang","orcid":"0000-0001-9845-3988","position":3,"is_corresponding":false},{"id":469033,"name":"Jessica C. Hsu","orcid":"0000-0002-3599-2834","position":4,"is_corresponding":false},{"id":327392,"name":"Xiuru Ji","orcid":null,"position":5,"is_corresponding":false},{"id":1485696,"name":"Shuping Li","orcid":"0000-0002-3139-882X","position":6,"is_corresponding":false},{"id":665094,"name":"Changjing Zuo","orcid":"0000-0002-2051-766X","position":7,"is_corresponding":false},{"id":244592,"name":"Weibo Cai","orcid":"0000-0003-4641-0833","position":8,"is_corresponding":false},{"id":304446,"name":"Dalong Ni","orcid":"0000-0001-6679-5414","position":9,"is_corresponding":false},{"id":1485693,"name":"Weiwei Su","orcid":"0009-0009-5630-7486","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:58:00.620755Z","pmid":"42421775","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":[]}