{"doi":"10.1002/btm2.10611","title":"Multimodal nanoparticle‐containing modified suberoylanilide hydroxamic acid polymer conjugates to mitigate immune dysfunction in severe inflammation","abstract":"Excessive immune activation and immunosuppression are opposing factors that contribute to the dysregulated innate and adaptive immune responses seen in severe inflammation and sepsis. Here, a novel analog of the histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA-OH), was incorporated into immunomodulatory poly(lactic acid)-based nanoparticles (iNP-SAHA) by employing a prodrug approach through the covalent modification of poly(lactic-co-glycolic acid) (PLGA) with SAHA-OH. iNP-SAHA formulation allowed for controlled incorporation and delivery of SAHA-OH from iNP-SAHA and treatment led to multimodal biological responses including significant reductions in proinflammatory cytokine secretions and gene expression, while increasing the survival of primary macrophages under lipopolysaccharide (LPS) challenge. Using a lethal LPS-induced endotoxemia mouse model of sepsis, iNP-SAHA administration improved the survival of mice in a dose-dependent manner and tended to improve survival at the lowest doses compared to iNP control. Further, iNP-SAHA reduced the levels of plasma proinflammatory cytokines and chemokines associated with sepsis more significantly than iNP and similarly improved inflammation-induced spleen and liver toxicity as iNP, supporting its potential polypharmacological activity. Collectively, iNP-SAHA offers a potential drug delivery approach to modulate the multifaceted inflammatory responses observed in diseases such as sepsis.","journal":"Bioengineering & Translational Medicine","year":2023,"id":361303,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":671938,"name":"Andrea L. Cottingham","orcid":"0000-0001-9067-2537","position":1,"is_corresponding":false},{"id":666774,"name":"Shruti Dharmaraj","orcid":"0000-0003-4257-9439","position":2,"is_corresponding":false},{"id":914605,"name":"Jacob R. Shaw","orcid":"0000-0002-5885-1006","position":3,"is_corresponding":false},{"id":472010,"name":"Jackline Joy Lasola","orcid":"0000-0002-1287-6830","position":4,"is_corresponding":false},{"id":932467,"name":"Christopher C. Goodis","orcid":null,"position":5,"is_corresponding":false},{"id":420254,"name":"Steven Fletcher","orcid":"0000-0002-4429-8334","position":6,"is_corresponding":false},{"id":260785,"name":"Ryan M. Pearson","orcid":"0000-0002-7857-0973","position":7,"is_corresponding":false},{"id":671940,"name":"Nhu Truong","orcid":"0000-0002-9562-1939","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:14:10.680991Z","pmid":"38193117","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":[]}