{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:46:31Z","timestamp":1790595991003,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation of China","award":["32471351"],"award-info":[{"award-number":["32471351"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The low immunogenicity and immune escape are bottlenecks for effective hepatocellular carcinoma (HCC) immunotherapy. We prepared and characterized a dual-target liposome complex, XA5508, by encapsulating the STING agonist cGAMP in liposomes and conjugating an anti-PD-L1 nanobody to the liposome surface. The anti-tumor effect and pharmacological mechanism of XA5508 were investigated using an in situ HCC mouse model. XA5508 can effectively inhibit in situ HCC with the characteristics of tumor-targeted delivery and sustained release of STING agonist cGAMP. The pharmacological mechanism study indicates that XA5508 activates the STING signaling pathway, increases the cytotoxicity of CD8+ T cells, reverses the immunosuppressive tumor microenvironment (TME) represented by M2-type macrophages, and transforms cold tumors into hot tumors. On the other hand, cGAMP induces the upregulation of PD-L1 expression in HCC, enhances the response of anti-PD-L1 nanobody (Nb) and the escape blockade of immune checkpoint PD-1\/PD-L1. XA5508 shows remarkable anti-tumor effects of STING agonist and anti-PD-L1 nanobody against HCC, providing an innovative strategy for the development of new drugs for HCC.<\/jats:p>","DOI":"10.3390\/ijms26178649","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T12:18:18Z","timestamp":1757074698000},"page":"8649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Study on the Efficacy and Pharmacological Mechanism of Liposome Complexes Containing STING Agonist and Anti-PD-L1 Nanobody in Inhibiting HCC"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3097-0894","authenticated-orcid":false,"given":"Xiaoqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangshi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Fudan University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103267","DOI":"10.3748\/wjg.v31.i14.103267","article-title":"Immune therapies in intermediate-advanced unresectable hepatocellular carcinoma: Changing the therapeutic landscape","volume":"31","author":"Biswas","year":"2025","journal-title":"World J. 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