{"doi":"10.1021/jacs.4c09831","title":"A Type I Photosensitizer-Polymersome Boosts Reactive Oxygen Species Generation by Forcing H-Aggregation for Amplifying STING Immunotherapy","abstract":"Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy. This structure promoted H-aggregation and intersystem crossing of NBS, resulting in a ∼ 3-fold amplification in superoxide anion and singlet oxygen generation. The photodynamic therapy directly damaged hypoxia tumor cells and stimulated the proliferation of NK cells and cytotoxic T lymphocytes, thereby sensitizing STING immunotherapy. A single systemic intravenous administration of PNBS/diABZI eradicated orthotopic mammary tumors in murine models, achieving long-term antitumor immune memory to inhibit tumor recurrence and metastasis and significantly improving long-term tumor-free survival. This work provides a design rule for boosting reactive oxygen species production by promoting the intersystem crossing process, highlighting the potential of Type I photosensitizer-polymer vehicles for augmenting STING immunotherapy.","journal":"Journal of the American Chemical Society","year":2024,"id":418028,"datarank":1.5435937435542928,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":0.9294420592209777,"self_endowment_contribution":0.6141516843333151,"citer_contribution":0.9294420592209777,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":56,"citers_with_citation_signal":38,"citers_with_endowment":38,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"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":1205315,"name":"Wen Ma","orcid":"0009-0004-9510-7579","position":1,"is_corresponding":false},{"id":236441,"name":"Zhèn Yáng","orcid":"0000-0003-4056-0347","position":2,"is_corresponding":false},{"id":477327,"name":"Dale O. Kiesewetter","orcid":"0000-0002-7679-1465","position":3,"is_corresponding":false},{"id":246614,"name":"Yicong Wu","orcid":"0000-0002-8819-7527","position":4,"is_corresponding":false},{"id":162048,"name":"Lixin Lang","orcid":null,"position":5,"is_corresponding":false},{"id":1205316,"name":"Guofeng Zhang","orcid":"0000-0001-5661-8430","position":6,"is_corresponding":false},{"id":300351,"name":"Sofia Nakuchima","orcid":null,"position":7,"is_corresponding":false},{"id":246601,"name":"Jiji Chen","orcid":"0000-0002-4426-3035","position":8,"is_corresponding":false},{"id":246595,"name":"Yijun Su","orcid":"0009-0001-4630-7863","position":9,"is_corresponding":false},{"id":109749,"name":"Sue Han","orcid":"0000-0001-8451-8592","position":10,"is_corresponding":false},{"id":1206204,"name":"Ling-Gang Wu","orcid":null,"position":11,"is_corresponding":false},{"id":344698,"name":"Albert J. Jin","orcid":"0000-0003-3826-1081","position":12,"is_corresponding":false},{"id":246407,"name":"Wei Huang","orcid":"0000-0001-7004-6408","position":13,"is_corresponding":false},{"id":880730,"name":"Zhixiong Wang","orcid":"0000-0003-0879-5728","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:02.483590Z","pmid":"39383053","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":[]}