{"doi":"10.2147/ijn.s390384","title":"Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection","abstract":"Purpose: Hepatocellular carcinoma (HCC) has limited treatment options, and modest survival after systemic chemotherapy or procedures such as transarterial chemoembolization (TACE). There is therefore a need to develop targeted therapies to address HCC. Gene therapies hold immense promise in treating a variety of diseases, including HCC, though delivery remains a critical hurdle. This study investigated a new approach of local delivery of polymeric nanoparticles (NPs) via intra-arterial injection for targeted local gene delivery to HCC tumors in an orthotopic rat liver tumor model. Methods: Poly(beta-amino ester) (PBAE) nanoparticles were formulated and assessed for GFP transfection in N1-S1 rat HCC cells in vitro. Optimized PBAE NPs were next administered to rats via intra-arterial injection with and without orthotopic HCC tumors, and both biodistribution and transfection were assessed. Results: In vitro transfection of PBAE NPs led to >50% transfected cells in adherent and suspension culture at a variety of doses and weight ratios. Administration of NPs via intra-arterial or intravenous injection demonstrated no transfection of healthy liver, while intra-arterial NP injection led to transfection of tumors in an orthotopic rat HCC model. Conclusion: Hepatic artery injection is a promising delivery approach for PBAE NPs and demonstrates increased targeted transfection of HCC tumors compared to intravenous administration, and offers a potential alternative to standard chemotherapies and TACE. This work demonstrates proof of concept for administration of polymeric PBAE nanoparticles via intra-arterial injection for gene delivery in rats.","journal":"International Journal of Nanomedicine","year":2023,"id":370074,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":670937,"name":"Camila Gadens Zamboni","orcid":"0000-0002-2365-7908","position":1,"is_corresponding":false},{"id":648145,"name":"Kathryn M Luly","orcid":"0000-0001-9020-9155","position":2,"is_corresponding":false},{"id":610991,"name":"Ling Li","orcid":"0000-0002-0087-3034","position":3,"is_corresponding":false},{"id":484337,"name":"Kathleen L. Gabrielson","orcid":"0000-0003-3901-4357","position":4,"is_corresponding":false},{"id":697966,"name":"Laboni F. Hassan","orcid":"0000-0002-0847-9867","position":5,"is_corresponding":false},{"id":697964,"name":"Nicholas P. Radant","orcid":"0000-0002-1037-6031","position":6,"is_corresponding":false},{"id":697965,"name":"Pranshu Bhardwaj","orcid":"0000-0003-2104-2085","position":7,"is_corresponding":false},{"id":270206,"name":"Florin M. Selaru","orcid":"0000-0001-7990-8238","position":8,"is_corresponding":false},{"id":7932,"name":"Martin G. Pomper","orcid":"0000-0001-6753-3010","position":9,"is_corresponding":false},{"id":239519,"name":"Jordan J. Green","orcid":"0000-0003-4176-3808","position":10,"is_corresponding":false},{"id":670936,"name":"Hannah J. Vaughan","orcid":"0000-0003-3463-9833","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:15:37.094100Z","pmid":"37197026","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":[]}