{"doi":"10.1021/acsami.1c04134","title":"Cross-linked Histone as a Nanocarrier for Gut Delivery of Hydrophobic Cargos","abstract":"Delivering hydrophobic molecules through the intestine can be challenging due to limited cargo solubility and the harsh biochemical environment of the stomach. Here, we show that a protein-based nanocarrier system based on the abundant protein histone and the natural cross-linker genipin can deliver hydrophobic cargos, such as dyes and therapeutic molecules, through the gastrointestinal tract. Using hydrophobic near-infrared dyes as model cargos, a panel of potential protein carriers was screened, and histone was identified as the one with the best loading capability. The resulting nanoparticles had a positive ζ potential and were mucoadhesive. Cross-linking of the amine-rich nanocarrier with genipin was particularly effective relative to other proteins and increased the stability of the system during incubation with pepsin. Cross-linking was required for successful delivery of a hydrophobic dye to the colon of mice after oral gavage. To assess the platform for therapeutic delivery, another hydrophobic model compound, curcumin, was delivered using cross-linked histone nanoparticles in a murine colitis model and significantly alleviated the disease. Taken together, these results demonstrate that histone is a cationic, mucoadhesive, and cross-linkable protein nanocarrier that can be considered for oral delivery.","journal":"ACS Applied Materials & Interfaces","year":2021,"id":196509,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":769107,"name":"Huijuan Zhang","orcid":"0000-0002-9017-0665","position":1,"is_corresponding":false},{"id":769108,"name":"Asmaa A. Zidan","orcid":"0000-0001-8248-8190","position":2,"is_corresponding":false},{"id":370085,"name":"Hailey I. Kilian","orcid":null,"position":3,"is_corresponding":false},{"id":279900,"name":"Wei‐Chiao Huang","orcid":null,"position":4,"is_corresponding":false},{"id":686326,"name":"Dushyant Jahagirdar","orcid":"0000-0003-4173-7378","position":5,"is_corresponding":false},{"id":277650,"name":"Joaquı́n Ortega","orcid":"0000-0002-9423-3344","position":6,"is_corresponding":false},{"id":368412,"name":"Jun Xia","orcid":"0000-0002-9864-7835","position":7,"is_corresponding":false},{"id":217892,"name":"Jonathan F. Lovell","orcid":"0000-0002-9052-884X","position":8,"is_corresponding":false},{"id":277649,"name":"Moustafa T. Mabrouk","orcid":"0000-0001-5912-2406","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-18T23:50:15.704473Z","pmid":"34082523","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":[]}