{"doi":"10.1007/s11095-022-03176-3","title":"Translational Modeling Identifies Synergy between Nanoparticle-Delivered miRNA-22 and Standard-of-Care Drugs in Triple-Negative Breast Cancer","abstract":"PURPOSE: Downregulation of miRNA-22 in triple-negative breast cancer (TNBC) is associated with upregulation of eukaryotic elongation 2 factor kinase (eEF2K) protein, which regulates tumor growth, chemoresistance, and tumor immunosurveillance. Moreover, exogenous administration of miRNA-22, loaded in nanoparticles to prevent degradation and improve tumor delivery (termed miRNA-22 nanotherapy), to suppress eEF2K production has shown potential as an investigational therapeutic agent in vivo. METHODS: To evaluate the translational potential of miRNA-22 nanotherapy, we developed a multiscale mechanistic model, calibrated to published in vivo data and extrapolated to the human scale, to describe and quantify the pharmacokinetics and pharmacodynamics of miRNA-22 in virtual patient populations. RESULTS: Our analysis revealed the dose-response relationship, suggested optimal treatment frequency for miRNA-22 nanotherapy, and highlighted key determinants of therapy response, from which combination with immune checkpoint inhibitors was identified as a candidate strategy for improving treatment outcomes. More importantly, drug synergy was identified between miRNA-22 and standard-of-care drugs against TNBC, providing a basis for rational therapeutic combinations for improved response CONCLUSIONS: The present study highlights the translational potential of miRNA-22 nanotherapy for TNBC in combination with standard-of-care drugs.","journal":"Pharmaceutical Research","year":2022,"id":250429,"datarank":0.4943755299006494,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.0,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":279154,"name":"Javier Ruiz-Ramírez","orcid":"0000-0002-6581-3286","position":1,"is_corresponding":false},{"id":279153,"name":"Joseph D. Butner","orcid":"0000-0003-0608-2580","position":2,"is_corresponding":false},{"id":371660,"name":"María J. Peláez","orcid":"0000-0003-2859-0762","position":3,"is_corresponding":false},{"id":247465,"name":"Caroline Chung","orcid":"0000-0002-9662-1519","position":4,"is_corresponding":false},{"id":691787,"name":"Anupama Hooda-Nehra","orcid":null,"position":5,"is_corresponding":false},{"id":315006,"name":"Renata Pasqualini","orcid":"0000-0002-4155-9324","position":6,"is_corresponding":false},{"id":315007,"name":"Wadih Arap","orcid":"0000-0002-8686-4584","position":7,"is_corresponding":false},{"id":279158,"name":"Vittorio Cristini","orcid":"0000-0002-7909-4278","position":8,"is_corresponding":false},{"id":44983,"name":"George A. Calin","orcid":"0000-0002-7427-0578","position":9,"is_corresponding":false},{"id":560187,"name":"Bülent Özpolat","orcid":"0000-0001-8602-7463","position":10,"is_corresponding":false},{"id":279159,"name":"Zhihui Wang","orcid":"0000-0001-6262-700X","position":11,"is_corresponding":false},{"id":279152,"name":"Prashant Dogra","orcid":"0000-0001-6722-7371","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:28.242323Z","pmid":"35294699","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":[]}