Journal
SMALL
Volume -, Issue -, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202300544
Keywords
Immunotherapy; positively charged liposomes; stimulator of interferon genes (STING); systemic delivery; tumor angiogenesis; vascular normalization
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Positively charged fusogenic liposomes loaded with a STING agonist are designed for systemic delivery and preferentially target the tumor microenvironment. This delivery system activates STING and induces robust anti-tumor T cell immunity within the tumor microenvironment.
Although stimulator of interferon genes (STING) agonists has shown great promise in preclinical studies, the clinical development of STING agonist therapy is challenged by its limited systemic delivery. Here, positively charged fusogenic liposomes loaded with a STING agonist (PoSTING) are designed for systemic delivery and to preferentially target the tumor microenvironment. When PoSTING is administered intravenously, it selectively targets not only tumor cells but also immune and tumor endothelial cells (ECs). In particular, delivery of STING agonists to tumor ECs normalizes abnormal tumor vasculatures, induces intratumoral STING activation, and elicits robust anti-tumor T cell immunity within the tumor microenvironment. Therefore, PoSTING can be used as a systemic delivery platform to overcome the limitations of using STING agonists in clinical trials.
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