{"doi":"10.1007/s11095-024-03762-7","title":"MR Molecular Image Guided Treatment of Pancreatic Cancer with Targeted ECO/miR-200c Nanoparticles in Immunocompetent Mouse Tumor Models","abstract":"OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is characterized by desmoplasia due to increased deposition of extracellular matrix (ECM) proteins. This work investigates the efficacy of targeted ECO/miR-200c nanoparticles (ELNP) on ECM remodeling in PDAC and tumor proliferation with MR molecular imaging (MRMI) with MT218 in immunocompetent mouse models. METHODS: The miR-200c mediated regulation of EMT markers was measured in PDAC cells in vitro. Wild-type mice bearing mutated KRAS-driven KPC subcutaneous or orthotopic tumors were dosed weekly with RGD-ELNP/miR-200c at 1 mg-RNA/kg for a total of 4 doses. We utilized MT218-MRMI to non-invasively monitor the alteration of tumor ECM EDN-FN levels by miR-200c and tumor response to the treatment. The changes were also validated by posthumous histopathology. RESULTS: Transfection of PDAC cells with ELNP/miR-200c downregulated the expression of FN1 and EDB-FN and some mesenchymal markers, inhibiting 3D spheroid formation and migration of KPC PDAC cells. RGD-ELNP/miR-200c treatment resulted in significant signal reduction in the MT218 enhanced MRMI images of both subcutaneous and orthotopic KPC tumors compared to those prior to treatment and treated with a non-specific control. MT218-MRMI results were suggestive of EDB-FN downregulation in tumors, which was later confirmed by immunohistochemistry. Tumor growth in subcutaneous tumors was significantly attenuated with RGD-ELNP/miR-200c and was an observed trend in orthotopic tumors. Substantial necrosis and remodeling were observed in both models treated with RGD-ELNP/miR-200c based on H&E staining. CONCLUSION: These results demonstrate the feasibility of RGD-ELNP/miR-200c in modulating PDAC ECM and restraining tumor growth and the utility of MT218-MRMI for non-invasively monitoring miR-200c efficacy.","journal":"Pharmaceutical Research","year":2024,"id":456395,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"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":702372,"name":"Ryan Hall","orcid":"0000-0003-2674-7834","position":1,"is_corresponding":false},{"id":1280822,"name":"Xueer Yuan","orcid":"0009-0001-5902-7895","position":2,"is_corresponding":false},{"id":1062114,"name":"Emma Hampson","orcid":null,"position":3,"is_corresponding":false},{"id":1281279,"name":"Augusta Halle","orcid":null,"position":4,"is_corresponding":false},{"id":1281280,"name":"Grace Yeung","orcid":null,"position":5,"is_corresponding":false},{"id":1281281,"name":"Kristen-Weber Bonk","orcid":null,"position":6,"is_corresponding":false},{"id":307984,"name":"Suneel Apte","orcid":"0000-0001-8441-1226","position":7,"is_corresponding":false},{"id":262927,"name":"Jordan M. Winter","orcid":"0000-0002-5200-6557","position":8,"is_corresponding":false},{"id":297923,"name":"Ruth A. Keri","orcid":"0000-0002-1640-3088","position":9,"is_corresponding":false},{"id":364020,"name":"Zheng‐Rong Lu","orcid":"0000-0001-8185-9519","position":10,"is_corresponding":false},{"id":655074,"name":"Victoria Laney","orcid":"0000-0003-1188-6591","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:03:27.785212Z","pmid":"39198318","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":[]}