{"doi":"10.3390/pharmaceutics15102479","title":"Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model","abstract":"Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body's immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed by intravenous administration of aPD-L1 labeled with a near-infrared fluorescent dye. The permeability of the BBB was evaluated using contrast-enhanced MRI in vivo, while fluorescence imaging and histological analysis were conducted on ex vivo pig brains. Results showed a significant 4.8-fold increase in MRI contrast-enhancement volume in FUS-targeted regions compared to nontargeted regions. FUS sonication enhanced aPD-L1 delivery by an average of 2.1-fold, according to fluorescence imaging. In vivo MRI and ex vivo staining revealed that the procedure did not cause significant acute tissue damage. These findings demonstrate that FUS-BBBO offers a noninvasive, localized, and safe delivery approach for ICI delivery in a large animal model, showcasing its potential for clinical translation.","journal":"Pharmaceutics","year":2023,"id":353141,"datarank":0.37059472187518533,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.04101103527475235,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.04101103527475235,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":7,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"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":575573,"name":"Chinwendu Chukwu","orcid":"0000-0001-9849-5328","position":1,"is_corresponding":false},{"id":1025875,"name":"Andrew H. Stark","orcid":"0009-0006-6672-2673","position":2,"is_corresponding":false},{"id":342974,"name":"Yimei Yue","orcid":"0000-0002-1592-1529","position":3,"is_corresponding":false},{"id":649415,"name":"Lu Xu","orcid":"0000-0003-4807-719X","position":4,"is_corresponding":false},{"id":702285,"name":"Chih-Yen Chien","orcid":"0000-0002-9529-2311","position":5,"is_corresponding":false},{"id":556941,"name":"Jinyun Yuan","orcid":"0000-0002-6559-1599","position":6,"is_corresponding":false},{"id":342976,"name":"Hong Chen","orcid":"0000-0003-1904-0857","position":7,"is_corresponding":false},{"id":866859,"name":"Siaka Fadera","orcid":null,"position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:58.542950Z","pmid":"37896238","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":[]}