{"doi":"10.1101/2023.09.01.555196","title":"Efficient ultrasound-mediated drug delivery to orthotopic liver tumors – Direct comparison of doxorubicin-loaded nanobubbles and microbubbles","abstract":"Abstract Liver metastasis is a major obstacle in treating aggressive cancers, and current therapeutic options often prove insufficient. To overcome these challenges, there has been growing interest in ultrasound-mediated drug delivery using lipid-shelled microbubbles (MBs) and nanobubbles (NBs) as promising strategies for enhancing drug delivery to tumors. Our previous work demonstrated the potential of Doxorubicin-loaded C 3 F 8 NBs (hDox-NB, 280 ± 123 nm) in improving cancer treatment in vitro using low-frequency ultrasound. In this study, we investigated the pharmacokinetics and biodistribution of sonicated hDox-NBs in orthotopic rat liver tumors. We compared their delivery and therapeutic efficiency with size-isolated MBs (hDox-MB, 1104 ± 373 nm). Results showed a similar accumulation of hDox in tumors treated with hDox-MBs and unfocused therapeutic ultrasound (hDox-MB+TUS) and hDox-NB+TUS. However, significantly increased apoptotic cell death in the tumor and fewer off-target apoptotic cells in the normal liver were found upon the treatment with hDox-NB+TUS. The tumor-to-liver apoptotic ratio was elevated 9.4-fold following treatment with hDox-NB+TUS compared to hDox-MB+TUS, suggesting that the therapeutic efficacy and specificity are significantly increased when using hDox-NB+TUS. These findings highlight the potential of this approach as a viable treatment modality for liver tumors. By elucidating the behavior of drug-loaded bubbles in vivo , we aim to contribute to developing more effective liver cancer treatments that could ultimately improve patient outcomes and decrease off-target side effects.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":397204,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"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":296389,"name":"Eric Abenojar","orcid":"0000-0002-2733-4006","position":1,"is_corresponding":false},{"id":988484,"name":"Michaela B. Cooley","orcid":"0000-0002-7955-3745","position":2,"is_corresponding":false},{"id":1172802,"name":"Felipe M. Berg","orcid":"0000-0001-6028-2503","position":3,"is_corresponding":false},{"id":886795,"name":"Claire Counil","orcid":"0000-0001-6051-5418","position":4,"is_corresponding":false},{"id":1173118,"name":"Amin Jafari Sojahrood","orcid":null,"position":5,"is_corresponding":false},{"id":1172803,"name":"Muhammad Saad Khan","orcid":"0000-0003-0044-5088","position":6,"is_corresponding":false},{"id":823593,"name":"Celina Yang","orcid":"0000-0002-9082-047X","position":7,"is_corresponding":false},{"id":1173119,"name":"Elizabeth Berndl","orcid":null,"position":8,"is_corresponding":false},{"id":337166,"name":"Marcin Golczak","orcid":"0000-0001-7477-4357","position":9,"is_corresponding":false},{"id":353755,"name":"Michael C. Kolios","orcid":"0000-0002-9994-8293","position":10,"is_corresponding":false},{"id":296390,"name":"Agata A. Exner","orcid":"0000-0003-3913-7066","position":11,"is_corresponding":false},{"id":486059,"name":"Pinunta Nittayacharn","orcid":"0000-0003-1114-4328","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":null,"created_at":"2026-07-19T01:19:35.497854Z","pmid":"37732235","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":[]}