{"doi":"10.1101/2024.07.15.603612","title":"Peptide Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell","abstract":"ABSTRACT Targeting of current therapies to treat or prevent loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off target effects. Current efforts to target the β-cell are limited by a lack of β-cell specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here we fabricate a novel tailorable polycaprolactone nanocapsule (NC) where multiple different targeting peptides can be interchangeably attached for β-cell specific delivery. Incorporation of a cationic surfactant in the NC shell allows for the attachment of Exendin-4 and an antibody for ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) for β-cell specific targeting. The average NC size ranges from 250-300nm with a polydispersity index under 0.2. The NCs are non-toxic, stable in media culture, and can be lyophilized and reconstituted. NCs coated with targeting peptide were taken up by human cadaveric islet β-cells and human stem cell-derived β-like cells (sBC) in vitro with a high level of specificity. Furthermore, NCs successfully delivered both hydrophobic and hydrophilic cargo to human β-cells. Finally, Exendin-4 coated NCs were stable and targeted the mouse pancreatic islet β-cell in vivo . Our unique NC design allows for the interchangeable coating of targeting peptides for future screening of targets with improved cell specificity. The ability to target and deliver thera-peutics to human pancreatic β-cells opens avenues for improved therapies and treatments to help the delay onset, prevent, or reverse T1D.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":501156,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":866232,"name":"Jessie M. Barra","orcid":"0000-0002-6456-9293","position":1,"is_corresponding":false},{"id":1350717,"name":"Kiefer Holcomb","orcid":null,"position":2,"is_corresponding":false},{"id":1316225,"name":"Andres Ocampo","orcid":null,"position":3,"is_corresponding":false},{"id":1316226,"name":"Ashton Fremin","orcid":null,"position":4,"is_corresponding":false},{"id":1315841,"name":"Jubril Olayinka Akolade","orcid":"0000-0001-5005-2085","position":5,"is_corresponding":false},{"id":1316227,"name":"A. M. Kratz","orcid":null,"position":6,"is_corresponding":false},{"id":1316228,"name":"Julianna K. Hays","orcid":null,"position":7,"is_corresponding":false},{"id":1316229,"name":"Ali Shilleh","orcid":null,"position":8,"is_corresponding":false},{"id":236999,"name":"David J. Hodson","orcid":"0000-0002-8641-8568","position":9,"is_corresponding":false},{"id":260273,"name":"Johannes Broichhagen","orcid":"0000-0003-3084-6595","position":10,"is_corresponding":false},{"id":262477,"name":"Holger A. Russ","orcid":"0000-0001-5117-2927","position":11,"is_corresponding":false},{"id":565712,"name":"Nikki L. Farnsworth","orcid":"0000-0002-9834-9168","position":12,"is_corresponding":false},{"id":1005182,"name":"Jillian Collins","orcid":"0000-0001-6468-3929","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:12.068207Z","pmid":"39071322","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":[]}