{"doi":"10.3390/pharmaceutics15041302","title":"Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer","abstract":"Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O2 and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (p < 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation.","journal":"Pharmaceutics","year":2023,"id":336169,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"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":947442,"name":"Hebah A. Falatah","orcid":"0000-0003-2195-4658","position":1,"is_corresponding":false},{"id":297780,"name":"Ji‐Bin Liu","orcid":"0000-0003-2979-9162","position":2,"is_corresponding":false},{"id":297773,"name":"Corinne E. Wessner","orcid":"0000-0002-5896-3841","position":3,"is_corresponding":false},{"id":681391,"name":"Brian E. Oeffinger","orcid":"0000-0002-1749-2852","position":4,"is_corresponding":false},{"id":947440,"name":"Ankit Rochani","orcid":"0000-0002-0119-0462","position":5,"is_corresponding":false},{"id":532969,"name":"Dennis B. Leeper","orcid":null,"position":6,"is_corresponding":false},{"id":297772,"name":"Flemming Forsberg","orcid":"0000-0003-2215-1371","position":7,"is_corresponding":false},{"id":326684,"name":"Joseph Curry","orcid":"0000-0001-9507-4237","position":8,"is_corresponding":false},{"id":947443,"name":"Gagan Kaushal","orcid":"0000-0002-6710-2963","position":9,"is_corresponding":false},{"id":297784,"name":"Scott W. Keith","orcid":"0000-0002-9428-1151","position":10,"is_corresponding":false},{"id":297779,"name":"Patrick O’Kane","orcid":"0000-0001-5038-934X","position":11,"is_corresponding":false},{"id":681392,"name":"Margaret A. Wheatley","orcid":"0000-0001-6917-8972","position":12,"is_corresponding":false},{"id":297771,"name":"John R. Eisenbrey","orcid":"0000-0001-6411-3424","position":13,"is_corresponding":false},{"id":684358,"name":"Quezia Lacerda","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:10:17.243221Z","pmid":"37111787","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":[]}