{"doi":"10.1101/2024.06.07.598019","title":"Polymeric Micellar Nanoparticles Enable Image-guided Drug Delivery in Solid Tumors","abstract":"ABSTRACT We report the development of a nanotechnology to co-deliver chemocoxib A with a reactive oxygen species (ROS)-activatable and COX-2 targeted pro-fluorescent probe, fluorocoxib Q (FQ) enabling real time visualization of COX-2 and CA drug delivery into solid cancers, using a di-block PPS 135 - b -POEGA 17 copolymer, selected for its intrinsic responsiveness to elevated reactive oxygen species (ROS), a key trait of the tumor microenvironment. FQ and CA were synthesized independently, then co-encapsulated within micellar PPS 135 - b -POEGA 17 co-polymeric nanoparticles (FQ-CA-NPs), and were assessed for cargo concentration, hydrodynamic diameter, zeta potential, and ROS-dependent cargo release. The uptake of FQ-CA-NPs in mouse mammary cancer cells and cargo release was assessed by fluorescence microscopy. Intravenous delivery of FQ-CA-NPs to mice harboring orthotopic mammary tumors, followed by vital optimal imaging, was used to assess delivery to tumors in vivo . The CA-FQ-NPs exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (ζ) of –1.59 ± 0.3 mV. Fluorescence microscopy showed ROS-dependent cargo release by FQ-CA-NPs in 4T1 cells, decreasing growth of 4T1 breast cancer cells, but not affecting growth of primary human mammary epithelial cells (HMECs). NP-derived fluorescence was detected in mammary tumors, but not in healthy organs. Tumor LC-MS/MS analysis identified both CA (2.38 nmol/g tumor tissue) and FQ (0.115 nmol/g tumor tissue), confirming the FQ-mediated image guidance of CA delivery in solid tumors. Thus, co-encapsulation of FQ and CA into micellar nanoparticles (FQ-CA-NPs) enabled ROS-sensitive drug release and COX-2-targeted visualization of solid tumors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":498339,"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":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1034368,"name":"Justin H. Lo","orcid":"0000-0002-2646-2495","position":1,"is_corresponding":false},{"id":294529,"name":"Mukesh Kumar Gupta","orcid":"0000-0002-9571-3454","position":2,"is_corresponding":false},{"id":1014687,"name":"Thomas Werfel","orcid":"0000-0002-7957-4917","position":3,"is_corresponding":false},{"id":1305916,"name":"Abu Asaduzzaman","orcid":"0000-0002-5041-1575","position":4,"is_corresponding":false},{"id":391732,"name":"Connor G. Oltman","orcid":null,"position":5,"is_corresponding":false},{"id":1207309,"name":"Eva F. Gbur","orcid":"0009-0006-4440-464X","position":6,"is_corresponding":false},{"id":1345393,"name":"Mohammed T. Mohyuddin","orcid":null,"position":7,"is_corresponding":false},{"id":1345108,"name":"Farhana Nazmin","orcid":"0009-0007-8157-6413","position":8,"is_corresponding":false},{"id":1345109,"name":"Saidur Rahman","orcid":"0000-0002-7992-5641","position":9,"is_corresponding":false},{"id":1345394,"name":"Ahan Jashim","orcid":null,"position":10,"is_corresponding":false},{"id":391731,"name":"Brenda C. Crews","orcid":null,"position":11,"is_corresponding":false},{"id":390887,"name":"Philip J. Kingsley","orcid":"0000-0002-5470-4340","position":12,"is_corresponding":false},{"id":318552,"name":"Lawrence J. Marnett","orcid":"0000-0002-7834-6285","position":13,"is_corresponding":false},{"id":294530,"name":"Craig L. Duvall","orcid":"0000-0003-3979-0620","position":14,"is_corresponding":false},{"id":511536,"name":"Rebecca S. Cook","orcid":"0000-0001-7749-5361","position":15,"is_corresponding":false},{"id":663955,"name":"Jashim Uddin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:09:42.181447Z","pmid":"38915607","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":[]}