Several studies have shown the importance of the cGAS-STING pathway in antigen-presenting cells for anti-cancer immunity. Cyclic GMP-AMP (cGAMP) – STING ligand is a negatively charged dinucleotide prone to degradation by hydrolases. Once administered in its soluble form, high doses are needed which in turn may cause side effects such as T cell apoptosis. Moreover, due to its negative charge, transfection of cGAMP into negatively-charged membrane cells is hampered. In order to achieve successful transfection and protection from enzymatic degradation there is a need for a suitable carrier for cGAMP. In this review, we therefore describe currently reported carriers for cGAMP, and correlate their characteristics to the effect they cause. To achieve targeted delivery to the tumor microenvironment, the route of administration and physicochemical parameters of the particles (containing a carrier and cGAMP) such as size and charge need to be determined. Therefore, the choice of the particle formulation and its impact on the preclinical outcome will be discussed.

多项研究表明，cGAS-STING 通路在抗原呈递细胞中对抗癌免疫的重要性。环状 GMP-AMP (cGAMP) – STING 配体是一种带负电荷的二核苷酸，易于被水解酶降解。一旦以其可溶形式给药，就需要高剂量，这反过来可能引起副作用，例如 T 细胞凋亡。此外，由于其负电荷，cGAMP 转染到带负电荷的膜细胞中受到阻碍。为了实现成功转染和防止酶促降解，需要合适的 cGAMP 载体。因此，在本综述中，我们描述了当前报告的 cGAMP 携带者，并将其特征与其造成的影响相关联。为了实现对肿瘤微环境的靶向递送，需要确定颗粒（含有载体和 cGAMP）的给药途径和物理化学参数，例如大小和电荷。因此，将讨论颗粒配方的选择及其对临床前结果的影响。