许多化疗药物可以诱导免疫原性细胞死亡（ICD），从而导致危险相关分子模式（DAMP）和肿瘤相关抗原的释放。该过程促进树突状细胞 (DC) 成熟和细胞毒性 T 淋巴细胞 (CTL) 浸润。然而，癌细胞可以采用多种机制来逃避宿主免疫系统。最近的研究表明，干扰素基因刺激剂（STING）激动剂，例如cGAMP，可以放大ICD触发的免疫反应，并增强免疫细胞向肿瘤微环境（TME）的浸润。基于这些发现，我们构建了阿霉素 (DOX) 和 cGAMP 共传递系统 (DOX/cGAMP@NPs)，用于黑色素瘤和三阴性乳腺癌 (TNBC) 的治疗。结果表明，DOX可以有效地破坏肿瘤并诱导ICD释放DAMPs。此外，在原位4T1肿瘤小鼠模型和皮下B16肿瘤小鼠模型中，cGAMP可以通过诱导I型干扰素和促炎细胞因子的分泌，促进DCs的成熟和CD8 T细胞的活化和浸润，从而放大诱导的抗肿瘤免疫反应。通过阿霉素。这一策略还促进了免疫抑制细胞的消耗，有可能减轻免疫抑制性 TME。总之，我们的研究强调 DOX 诱导的 ICD 与 cGAMP 的免疫增强特性的结合对未来的研究和临床应用具有重要意义。版权所有 © 2024。由 Elsevier B.V. 出版。

Many chemotherapeutic agents can induce immunogenic cell death (ICD), which leads to the release of danger-associated molecular patterns (DAMPs) and tumor-associated antigens. This process promotes dendritic cells (DCs) maturation and cytotoxic T lymphocyte (CTL) infiltration. However, cancer cells can employ diverse mechanisms to evade the host immune system. Recent studies have shown that stimulator of interferon genes (STING) agonists, such as cGAMP, can amplify ICD-triggered immune responses and enhance the infiltration of immune cells into the tumor microenvironment (TME). Building upon these findings, we constructed a doxorubicin (DOX) and cGAMP co-delivery system (DOX/cGAMP@NPs) for melanoma and triple-negative breast cancer (TNBC) therapy. The results demonstrated that DOX could effectively destroy tumors and induce the release of DAMPs by ICD. Furthermore, in orthotopic 4T1 tumors mice model and subcutaneous B16 tumor mice model, cGAMP could promote the maturation of DCs and CD8+ T cell activation and infiltration by inducing the secretion of type I interferons and pro-inflammation cytokine, which amplified the antitumor immune response induced by DOX. This strategy also promoted the depletion of immunosuppressive cells, potentially alleviating the immunosuppressive TME. In conclusion, our study highlights the combination of DOX-induced ICD and the immune-enhancing properties of cGAMP holds significant implications for future research and clinical applications.Copyright © 2024. Published by Elsevier B.V.