{"doi":"10.1016/j.bioactmat.2020.04.011","title":"High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma","abstract":"Glioblastoma (GBM), the deadliest form of brain cancer, presents long-standing problems due to its localization. Chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a powerful strategy to treat cancer. IL-13-receptor-α2 (IL13Rα2), present in over 75% of GBMs, has been recognized as an attractive candidate for anti-glioblastoma therapy. Here, we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent, therapeutic nanoparticles and CAR T cells modified with a targeted-quadruple-mutant of IL13 (TQM-13) shown to have high binding affinity to IL13Rα2-expressing glioblastoma cells with low off-target toxicity. Azide-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile, selective, and high-yielding clicking of the nanoparticles. Nanoparticles clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for in vivo delivery. T cells clicked with doxorubicin-loaded nanoparticles showed a higher cytotoxic effect in vitro compared to bare T cells. In vitro and in vivo T cells expressing TQM-13 served as delivery shuttles for nanoparticles and significantly increased the number of nanoparticles reaching brain tumors compared to nanoparticles alone. This work represents a new platform to allow the delivery of therapeutic nanoparticles and T cells to solid tumors.","journal":"Bioactive Materials","year":2020,"id":60761,"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":60,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322065,"name":"Virginia Aragon‐Sanabria","orcid":null,"position":1,"is_corresponding":false},{"id":320852,"name":"Lauren N. Randolph","orcid":"0000-0002-1628-8673","position":2,"is_corresponding":false},{"id":322066,"name":"Hali Jiang","orcid":null,"position":3,"is_corresponding":false},{"id":320853,"name":"Joshua Reynolds","orcid":"0000-0001-6680-5993","position":4,"is_corresponding":false},{"id":322067,"name":"Becky Webb","orcid":null,"position":5,"is_corresponding":false},{"id":320854,"name":"Achuthamangalam B. Madhankumar","orcid":"0000-0003-0405-9424","position":6,"is_corresponding":false},{"id":270356,"name":"Xiaojun Lian","orcid":"0000-0002-9161-1004","position":7,"is_corresponding":false},{"id":320855,"name":"James R. Connor","orcid":"0000-0003-0481-8240","position":8,"is_corresponding":false},{"id":320856,"name":"Jian Yang","orcid":"0000-0003-0695-828X","position":9,"is_corresponding":false},{"id":320857,"name":"Cheng Dong","orcid":"0000-0002-7760-4692","position":10,"is_corresponding":false},{"id":322064,"name":"Gloria B. Kim","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T21:09:05.493770Z","pmid":"32405577","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":[]}