{"doi":"10.1126/sciadv.abj1577","title":"Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis","abstract":"Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.","journal":"Science Advances","year":2021,"id":154715,"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":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"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":655364,"name":"Hyungjun Kim","orcid":"0000-0003-3958-7999","position":1,"is_corresponding":false},{"id":268562,"name":"Nader S. Abutaleb","orcid":"0000-0003-1730-4150","position":2,"is_corresponding":false},{"id":655365,"name":"Alexandra M. Dieterly","orcid":"0000-0001-7819-1503","position":3,"is_corresponding":false},{"id":655366,"name":"Maie S. Taha","orcid":"0000-0003-1549-3867","position":4,"is_corresponding":false},{"id":656152,"name":"Michael D. Tsifansky","orcid":null,"position":5,"is_corresponding":false},{"id":655367,"name":"L. Tiffany Lyle","orcid":"0000-0003-1588-4876","position":6,"is_corresponding":false},{"id":106917,"name":"Mohamed N. Seleem","orcid":"0000-0003-0939-0458","position":7,"is_corresponding":false},{"id":499536,"name":"Yoon Yeo","orcid":"0000-0001-9505-7701","position":8,"is_corresponding":false},{"id":655363,"name":"Simseok A. Yuk","orcid":"0000-0002-6610-4940","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:43:54.469024Z","pmid":"34362742","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":[]}