{"doi":"10.1073/pnas.251662398","title":"Targeting endothelium and its dynamic caveolae for tissue-specific transcytosis\n                    <i>in vivo</i>\n                    : A pathway to overcome cell barriers to drug and gene delivery","abstract":"<jats:p>\n                    Site-directed pharmacodelivery is a desirable but elusive goal. Endothelium and epithelium create formidable barriers to endogenous molecules as well as targeted therapies\n                    <jats:italic>in vivo</jats:italic>\n                    . Caveolae provide a possible, yet unproven, transcellular pathway to overcome such barriers. By using an antibody- and subfractionation-based strategy, we generated a monoclonal antibody specific for lung caveolae (TX3.833) that targets rat lungs after i.v. injection (up to 89% of dose in 30 min). Unlike control antibodies (nonbinding or to lipid rafts), TX3.833 targets lung caveolae that bud to form free vesicles for selective and quantal transendothelial transport to underlying tissue cells\n                    <jats:italic>in vivo</jats:italic>\n                    . Rapid sequential transcytosis can occur to the alveolar air space via epithelial caveolae. Conjugation to TX3.833 increases drug delivery to the lung up to 172-fold and achieves rapid, localized bioefficacy. We conclude that: (\n                    <jats:italic>i</jats:italic>\n                    ) molecular heterogeneity of the endothelium and its caveolae permits vascular targeting to achieve theoretical expectations of tissue-specific delivery and bioefficacy; (\n                    <jats:italic>ii</jats:italic>\n                    ) caveolae can mediate selective transcytosis\n                    <jats:italic>in vivo</jats:italic>\n                    ; and (\n                    <jats:italic>iii</jats:italic>\n                    ) targeting caveolae may provide a tissue-specific pathway for overcoming key cell barriers to many drug and gene therapies\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2002,"id":607970,"datarank":0.8048964022532777,"base_score":5.365976015021851,"endowment":5.365976015021851,"self_citation_contribution":0.8048964022532777,"citation_network_contribution":0.0,"self_endowment_contribution":0.8048964022532777,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":213,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1561216,"name":"Xiang-Yang Tan","orcid":null,"position":1,"is_corresponding":false},{"id":1561218,"name":"Phil Oh","orcid":null,"position":2,"is_corresponding":false},{"id":158275,"name":"Jan E. Schnitzer","orcid":null,"position":3,"is_corresponding":false},{"id":1561213,"name":"Deirdre P. McIntosh","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting endothelium and its dynamic caveolae for tissue-specific transcytosis\n                    <i>in vivo</i>\n                    : A pathway to overcome cell barriers to drug and gene delivery","abstract":"<jats:p>\n                    Site-directed pharmacodelivery is a desirable but elusive goal. Endothelium and epithelium create formidable barriers to endogenous molecules as well as targeted therapies\n                    <jats:italic>in vivo</jats:italic>\n                    . Caveolae provide a possible, yet unproven, transcellular pathway to overcome such barriers. By using an antibody- and subfractionation-based strategy, we generated a monoclonal antibody specific for lung caveolae (TX3.833) that targets rat lungs after i.v. injection (up to 89% of dose in 30 min). Unlike control antibodies (nonbinding or to lipid rafts), TX3.833 targets lung caveolae that bud to form free vesicles for selective and quantal transendothelial transport to underlying tissue cells\n                    <jats:italic>in vivo</jats:italic>\n                    . Rapid sequential transcytosis can occur to the alveolar air space via epithelial caveolae. Conjugation to TX3.833 increases drug delivery to the lung up to 172-fold and achieves rapid, localized bioefficacy. We conclude that: (\n                    <jats:italic>i</jats:italic>\n                    ) molecular heterogeneity of the endothelium and its caveolae permits vascular targeting to achieve theoretical expectations of tissue-specific delivery and bioefficacy; (\n                    <jats:italic>ii</jats:italic>\n                    ) caveolae can mediate selective transcytosis\n                    <jats:italic>in vivo</jats:italic>\n                    ; and (\n                    <jats:italic>iii</jats:italic>\n                    ) targeting caveolae may provide a tissue-specific pathway for overcoming key cell barriers to many drug and gene therapies\n                    <jats:italic>in vivo</jats:italic>\n                    .\n                  </jats:p>","is_dataset_classified":null,"base_score":5.365976015021851,"endowment":5.365976015021851,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11854497","pmcid":"PMC122308","openalex_id":"https://openalex.org/W2088812802","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL52766","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL58216","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL052766","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL058216","title":null}],"total_grants":4,"fwci":6.1603,"citation_percentile":0.97389725,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":6},{"year":2014,"count":4},{"year":2015,"count":11},{"year":2016,"count":5},{"year":2017,"count":8},{"year":2018,"count":5},{"year":2019,"count":2},{"year":2020,"count":5},{"year":2021,"count":4},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":9},{"year":2025,"count":6}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/122308","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/122308","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.251662398","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.251662398","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11854497","host_type":"repository"}],"fields_of_study":["Caveolin-1 and cellular processes","Blood disorders and treatments","Erythrocyte Function and Pathophysiology","Animals","Antibodies, Monoclonal","Biological Transport","Blotting, Western","Caveolae","Endothelium, Vascular","Enzyme-Linked Immunosorbent Assay","Gene Transfer Techniques","Genetic Vectors","Immunoglobulin G","In Situ Hybridization","Lung","Perfusion","Rats","Time Factors","Tissue Distribution"],"mesh_terms":["Animals","Antibodies, Monoclonal","Biological Transport","Endothelium, Vascular","Enzyme-Linked Immunosorbent Assay","Genetic Vectors","Immunoglobulin G","Lung","Perfusion","Time Factors","Tissue Distribution","Blotting, Western","In Situ Hybridization","Gene Transfer Techniques","Caveolae","Rats"],"keywords":["Transcytosis","Caveolae","In vivo","Cell biology","Biology","Endothelium","Paracellular transport","Drug delivery","Cell","Endocytosis","Chemistry","Signal transduction","Biochemistry","Membrane"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T07:17:55.851297Z","pmid":null,"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":[]}