{"doi":"10.1002/advs.202307940","title":"In Situ Formation of Fibronectin‐Enriched Protein Corona on Epigenetic Nanocarrier for Enhanced Synthetic Lethal Therapy","abstract":"PARP inhibitors (PARPi)-based synthetic lethal therapy demonstrates limited efficacy for most cancer types that are homologous recombination (HR) proficient. To potentiate the PARPi application, a nanocarrier based on 5-azacytidine (AZA)-conjugated polymer (PAZA) for the codelivery of AZA and a PARP inhibitor, BMN673 (BMN) is developed. AZA conjugation significantly decreased the nanoparticle (NP) size and increased BMN loading. Molecular dynamics simulation and experimental validations shed mechanistic insights into the self-assembly of effective NPs. The small PAZA NPs demonstrated higher efficiency of tumor targeting and penetration than larger NPs, which is mediated by a new mechanism of active targeting that involves the recruitment of fibronectin from serum proteins following systemic administration of PAZA NPs. Furthermore, it is found that PAZA carrier sensitize the HR-proficient nonsmall cell lung cancer (NSCLC) to BMN, a combination therapy that is more effective at a lower AZA/BMN dosage. To investigate the underlying mechanism, the tumor immune microenvironment and various gene expressions by RNAseq are explored. Moreover, the BMN/PAZA combination increased the immunogenicity and synergized with PD-1 antibody in improving the overall therapeutic effect in an orthotopic model of lung cancer (LLC).","journal":"Advanced Science","year":2024,"id":432055,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355119,"name":"Zhuoya Wan","orcid":"0000-0001-6747-7100","position":1,"is_corresponding":false},{"id":459942,"name":"Pengfei Ren","orcid":"0009-0002-9517-0813","position":2,"is_corresponding":false},{"id":459943,"name":"Bei Zhang","orcid":"0000-0002-4599-581X","position":3,"is_corresponding":false},{"id":459944,"name":"Yixian Huang","orcid":"0009-0004-2601-2875","position":4,"is_corresponding":false},{"id":363540,"name":"Raymond E. West","orcid":"0000-0002-6362-8837","position":5,"is_corresponding":false},{"id":355116,"name":"Haozhe Huang","orcid":"0000-0001-6765-5931","position":6,"is_corresponding":false},{"id":645870,"name":"Yuang Chen","orcid":"0000-0001-8733-3948","position":7,"is_corresponding":false},{"id":363543,"name":"Thomas D. Nolin","orcid":"0000-0003-4339-1382","position":8,"is_corresponding":false},{"id":355801,"name":"Wen Xie","orcid":"0000-0003-3967-155X","position":9,"is_corresponding":false},{"id":86256,"name":"Junmei Wang","orcid":"0000-0002-9607-8229","position":10,"is_corresponding":false},{"id":6554,"name":"Song Li","orcid":"0000-0002-6427-3986","position":11,"is_corresponding":false},{"id":355115,"name":"Jingjing Sun","orcid":"0000-0002-6230-1015","position":12,"is_corresponding":false},{"id":355114,"name":"Zhangyi Luo","orcid":"0009-0007-5791-4013","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:59:35.267142Z","pmid":"38482976","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":[]}