{"doi":"10.2147/ijn.s462213","title":"Delivery of a STING Agonist Using Lipid Nanoparticles Inhibits Pancreatic Cancer Growth","abstract":"Introduction: The tumor microenvironment (TME) of pancreatic cancer is highly immunosuppressive and characterized by a large number of cancer-associated fibroblasts, myeloid-derived suppressor cells, and regulatory T cells. Stimulator of interferon genes (STING) is an endoplasmic reticulum receptor that plays a critical role in immunity. STING agonists have demonstrated the ability to inflame the TME, reduce tumor burden, and confer anti-tumor activity in mouse models. 2'3' cyclic guanosine monophosphate adenosine monophosphate (2'3'-cGAMP) is a high-affinity endogenous ligand of STING. However, delivering cGAMP to antigen-presenting cells and tumor cells within the cytosol remains challenging due to membrane impermeability and poor stability. Methods: In this study, we encapsulated 2'3'-cGAMP in a lipid nanoparticle (cGAMP-LNP) designed for efficient cellular delivery. We assessed the properties of the nanoparticles using a series of in-vitro studies designed to evaluate their cellular uptake, cytosolic release, and minimal cytotoxicity. Furthermore, we examined the nanoparticle's anti-tumor effect in a syngeneic mouse model of pancreatic cancer. Results: The lipid platform significantly increased the cellular uptake of 2'3'-cGAMP. cGAMP-LNP exhibited promising antitumor activity in the syngeneic mouse model of pancreatic cancer. Discussion: The LNP platform shows promise for delivering exogenous 2'3'-cGAMP or its derivatives in cancer therapy.","journal":"International Journal of Nanomedicine","year":2024,"id":426594,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"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":620465,"name":"Pratikkumar Patel","orcid":"0000-0003-4255-4442","position":1,"is_corresponding":false},{"id":716391,"name":"Umar‐Farouk Mamani","orcid":null,"position":2,"is_corresponding":false},{"id":877217,"name":"Yuhan Guo","orcid":"0009-0002-7088-4940","position":3,"is_corresponding":false},{"id":1225990,"name":"Sushil Koirala","orcid":"0000-0002-4576-4747","position":4,"is_corresponding":false},{"id":697933,"name":"Chien‐Yu Lin","orcid":"0009-0007-3865-0630","position":5,"is_corresponding":false},{"id":867529,"name":"Mohammed Alahmari","orcid":"0000-0002-5608-9572","position":6,"is_corresponding":false},{"id":716392,"name":"Evanthia Omoscharka","orcid":null,"position":7,"is_corresponding":false},{"id":263787,"name":"Kun Cheng","orcid":"0000-0001-9544-4680","position":8,"is_corresponding":false},{"id":1226646,"name":"Sherin Shaji","orcid":null,"position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:58:42.796720Z","pmid":"39220196","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":[]}