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Apoptotic Body-Mediated Intracellular Delivery Strategy for Enhanced STING Activation and Improved Tumor Immunogenicity

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posted on 2022-03-07, 13:36 authored by Peng Bao, Zi-Tong Zheng, Jing-Jie Ye, Xian-Zheng Zhang
Agonists of stimulators of interferon genes (STING) are a promising class of immunotherapeutics that trigger potent innate immunity. However, the therapeutic efficacy of conventional STING agonists, such as 2′,3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), is severely restricted to poor cytosolic delivery and lacks the capacity to promote the recognition of tumor-specific antigens. Here, we tackle these challenges through a nanovaccine platform based on Fenton-reactive and STING-activating nanoparticles, synergistically contributing to the generation of tumor-cell-derived apoptotic bodies (ABs). ABs loaded with exogenous cGAMP are readily phagocytosed by antigen-presenting cells (APCs), as a Trojan horse for rendering tumor cells with high immunogenicity instead of a noninflammatory response. This leads to enhanced STING activation and an improved tumor-specific antigen presentation ability, boosting the adaptive immunity in collaboration with innate immune. The strategy of exploiting a metal-based nanovaccine platform possesses great potential to be clinically translated into a trinitarian system of diagnosis, treatment, and prognosis.

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