{"doi":"10.1002/adtp.202100100","title":"Nanoparticle‐Mediated Delivery of Micheliolide Analogs to Eliminate Leukemic Stem Cells in the Bone Marrow","abstract":"Abstract Micheliolide (MCL) is a naturally occurring sesquiterpene lactone that selectively targets leukemic stem cells (LSCs), which persist after conventional chemotherapy for myeloid leukemias, leading to disease relapse. To overcome modest MCL cytotoxicity, analogs with ≈two–threefold greater cytotoxicity against LSCs are synthesized via late‐stage chemoenzymatic C─H functionalization. To enhance bone marrow delivery, MCL analogs are entrapped within bone‐targeted polymeric nanoparticles (NPs). Robust drug loading capacities of up to 20% (mg drug mg −1 NP) are obtained, with release dominated by analog hydrophobicity. NPs loaded with a hydrolytically stable analog are tested in a leukemic mouse model. Median survival improved by 13% and bone marrow LSCs are decreased 34‐fold following NP MCL treatments versus controls. Additionally, selective leukemic cell and LSC cytotoxicity of the treatment versus normal hematopoietic cells is observed. Overall, these studies demonstrate that MCL‐based antileukemic agents combined with bone‐targeted NPs offer a promising strategy for eradicating LSCs.","journal":"Advanced Therapeutics","year":2021,"id":198679,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"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":238458,"name":"Hanan Alwaseem","orcid":"0000-0002-4946-1436","position":1,"is_corresponding":false},{"id":774502,"name":"Michele Counts","orcid":null,"position":2,"is_corresponding":false},{"id":774011,"name":"Andrew Bortz","orcid":"0000-0003-1993-3831","position":3,"is_corresponding":false},{"id":689599,"name":"Simone Giovani","orcid":"0000-0003-0229-7816","position":4,"is_corresponding":false},{"id":774012,"name":"Benjamin J. Frisch","orcid":"0000-0003-0048-8491","position":5,"is_corresponding":false},{"id":270966,"name":"Rudi Fasan","orcid":"0000-0003-4636-9578","position":6,"is_corresponding":false},{"id":303880,"name":"Danielle S. W. Benoit","orcid":"0000-0001-7137-8164","position":7,"is_corresponding":false},{"id":708884,"name":"Marian A. Ackun‐Farmmer","orcid":"0000-0003-3081-5115","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:50:31.857233Z","pmid":"35097186","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":[]}