{"doi":"10.1158/0008-5472.c.6512452","title":"Data from Optimized Doxorubicin Chemotherapy for Diffuse Large B-cell Lymphoma Exploits Nanocarrier Delivery to Transferrin Receptors","abstract":"<div>Abstract<p>New treatments are needed to address persistent unmet clinical needs for diffuse large B-cell lymphoma (DLBCL). Overexpression of transferrin receptor 1 (TFR1) is common across cancer and permits cell-surface targeting of specific therapies in preclinical and clinical studies of various solid tumors. Here, we developed novel nanocarrier delivery of chemotherapy via TFR1-mediated endocytosis, assessing this target for the first time in DLBCL. Analysis of published datasets showed novel association of increased TFR1 expression with high-risk DLBCL cases. Carbon–nitride dots (CND) are emerging nanoparticles with excellent <i>in vivo</i> stability and distribution and are adaptable to covalent conjugation with multiple substrates. <i>In vitro</i>, linking doxorubicin (Dox) and transferrin (TF) to CND (CND–Dox–TF, CDT) was 10–100 times more potent than Dox against DLBCL cell lines. Gain- and loss-of-function studies and fluorescent confocal microscopy confirmed dependence of these effects on TFR1-mediated endocytosis. In contrast with previous therapeutics directly linking Dox and TF, cytotoxicity of CDT resulted from nuclear entry by Dox, promoting double-stranded DNA breaks and apoptosis. CDT proved safe to administer <i>in vivo</i>, and when incorporated into standard frontline chemoimmunotherapy in place of Dox, it improved overall survival by controlling patient-derived xenograft tumors with greatly reduced host toxicities. Nanocarrier-mediated Dox delivery to cell-surface TFR1, therefore, warrants optimization as a potential new therapeutic option in DLBCL.</p>Significance:<p>Targeted nanoparticle delivery of doxorubicin chemotherapy via the TRF1 receptor presents a new opportunity against high-risk DLBCL tumors using potency and precision.</p></div>","journal":null,"year":2023,"id":404449,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":504842,"name":"Piumi Y. Liyanage","orcid":"0000-0002-6760-0049","position":1,"is_corresponding":false},{"id":682149,"name":"Asaad Trabolsi","orcid":"0000-0002-2479-1797","position":2,"is_corresponding":false},{"id":706022,"name":"Evan R. Roberts","orcid":null,"position":3,"is_corresponding":false},{"id":705454,"name":"Lingxiao Li","orcid":"0000-0003-1628-2738","position":4,"is_corresponding":false},{"id":705455,"name":"Braulio C.L.B. Ferreira","orcid":"0000-0001-8242-0399","position":5,"is_corresponding":false},{"id":1182307,"name":"Zhen Gao","orcid":"0000-0001-5482-4505","position":6,"is_corresponding":false},{"id":620649,"name":"Yuguang Ban","orcid":"0000-0002-2874-0647","position":7,"is_corresponding":false},{"id":705456,"name":"Austin D. Newsam","orcid":"0000-0002-8926-6539","position":8,"is_corresponding":false},{"id":318551,"name":"Melissa W. Taggart","orcid":"0000-0002-7803-9904","position":9,"is_corresponding":false},{"id":355510,"name":"Francisco Vega","orcid":"0000-0001-5956-452X","position":10,"is_corresponding":false},{"id":675334,"name":"Daniel Bilbao","orcid":"0000-0003-1630-8811","position":11,"is_corresponding":false},{"id":504845,"name":"Roger M. Leblanc","orcid":"0000-0001-8836-8042","position":12,"is_corresponding":false},{"id":315054,"name":"Jonathan H. Schatz","orcid":"0000-0003-1842-228X","position":13,"is_corresponding":false},{"id":705453,"name":"Artavazd Arumov","orcid":"0000-0002-9520-2777","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:44.591715Z","pmid":null,"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":[]}