{"doi":"10.1016/j.stemcr.2023.08.005","title":"Protein-encapsulated doxorubicin reduces cardiotoxicity in hiPSC-cardiomyocytes and cardiac spheroids while maintaining anticancer efficacy","abstract":"The chemotherapeutic doxorubicin (DOX) detrimentally impacts the heart during cancer treatment. This necessitates development of non-cardiotoxic delivery systems that retain DOX anticancer efficacy. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), endothelial cells (hiPSC-ECs), cardiac fibroblasts (hiPSC-CFs), multi-lineage cardiac spheroids (hiPSC-CSs), patient-specific hiPSCs, and multiple human cancer cell lines to compare the anticancer efficacy and reduced cardiotoxicity of single protein encapsulated DOX (SPEDOX-6), to standard unformulated (UF) DOX. Cell viability assays and immunostaining in human cancer cells, hiPSC-ECs, and hiPSC-CFs revealed robust uptake of SPEDOX-6 and efficacy in killing these proliferative cell types. In contrast, hiPSC-CMs and hiPSC-CSs exhibited substantially lower cytotoxicity during SPEDOX-6 treatment compared with UF DOX. SPEDOX-6-treated hiPSC-CMs and hiPSC-CSs maintained their functionality, as indicated by sarcomere contractility assessment, calcium imaging, multielectrode arrays, and RNA sequencing. This study demonstrates the potential of SPEDOX-6 to alleviate cardiotoxic side effects associated with UF DOX, while maintaining its anticancer potency.","journal":"Stem Cell Reports","year":2023,"id":329002,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"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":1051039,"name":"Bowen Gao","orcid":"0000-0003-4009-2299","position":1,"is_corresponding":false},{"id":1051040,"name":"Maedeh Mozneb","orcid":"0000-0003-3472-3859","position":2,"is_corresponding":false},{"id":1051530,"name":"Stephany Pohlman","orcid":null,"position":3,"is_corresponding":false},{"id":1051041,"name":"Romina B. Cejas","orcid":"0000-0002-5484-4722","position":4,"is_corresponding":false},{"id":930822,"name":"Qizhi Liu","orcid":"0009-0001-6060-8435","position":5,"is_corresponding":false},{"id":566277,"name":"Faqing Huang","orcid":"0000-0001-8185-7097","position":6,"is_corresponding":false},{"id":1051042,"name":"Changjun Yu","orcid":"0000-0002-5722-6751","position":7,"is_corresponding":false},{"id":846702,"name":"Yi Zhang","orcid":"0000-0001-6223-4724","position":8,"is_corresponding":false},{"id":696527,"name":"Xuemo Fan","orcid":"0000-0002-4410-3867","position":9,"is_corresponding":false},{"id":1051531,"name":"Amelia Jenkins","orcid":null,"position":10,"is_corresponding":false},{"id":314504,"name":"Armando E. Giuliano","orcid":"0000-0002-5421-945X","position":11,"is_corresponding":false},{"id":245967,"name":"Paul W. Burridge","orcid":"0000-0001-9616-0006","position":12,"is_corresponding":false},{"id":241094,"name":"Xiaojiang Cui","orcid":"0000-0002-6843-736X","position":13,"is_corresponding":false},{"id":232367,"name":"Arun Sharma","orcid":"0000-0002-0607-5455","position":14,"is_corresponding":false},{"id":1051529,"name":"Madelyn Arzt","orcid":null,"position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37657447","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":[]}