The immunosuppressive tumor microenvironment (TME) in solid tumors often impedes the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs), as a promising cancer vaccine that can potently stimulate immune responses, have garnered interest as a potential platform for cancer therapy. However, the low yield of OMVs limits their utilization. To address this limitation, we developed a novel approach to synthesize OMV-like multifunctional synthetic bacterial vesicles (SBVs) by pretreating bacteria with ampicillin and lysing them through sonication. Compared to OMVs, the yield of SBVs increased by 40 times. Additionally, the unique synthesis process of SBVs allows for the encapsulation of bacterial intracellular contents, endowing SBVs with the capability of delivering catalase (CAT) for tumor hypoxia relief and activating the host cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. To overcome the toxicity of lipopolysaccharide (LPS) on the SBVs surface, we decorated SBVs with a biocompatible polydopamine (PDA) shell, which allowed TME reprogramming using SBVs to be conducted without adverse side effects. Additionally, the photosensitizer indocyanine green (ICG) was loaded into the PDA shell to induce immunogenic cell death and further improve the efficacy of immunotherapy. In summary, the SBVs-based therapeutic platform SBV@PDA/ICG (SBV@P/I) can synergistically elicit safe and potent tumor-specific antitumor responses through combined immunotherapy and phototherapy.

中文翻译：

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工程细菌膜囊泡作为安全高效的纳米加热器，可重新编程肿瘤微环境以增强免疫治疗


实体瘤中的免疫抑制肿瘤微环境（TME）通常会阻碍免疫治疗的疗效。细菌外膜囊泡（OMV）作为一种有前途的癌症疫苗，可以有效刺激免疫反应，作为癌症治疗的潜在平台引起了人们的兴趣。然而，OMV 的低产率限制了它们的利用。为了解决这一限制，我们开发了一种新方法，通过用氨苄青霉素预处理细菌并通过超声处理裂解它们来合成类似 OMV 的多功能合成细菌囊泡 (SBV)。与OMV相比，SBV的产量提高了40倍。此外，SBV 独特的合成过程允许封装细菌细胞内内容物，赋予 SBV 传递过氧化氢酶（CAT）以缓解肿瘤缺氧并激活宿主环 GMP-AMP 合酶（cGAS）/干扰素基因刺激剂的能力。 STING）信号通路。为了克服 SBV 表面脂多糖 (LPS) 的毒性，我们用生物相容性聚多巴胺 (PDA) 外壳修饰 SBV，从而允许使用 SBV 进行 TME 重编程，而不会产生不良副作用。此外，将光敏剂吲哚菁绿（ICG）加载到PDA外壳中，诱导免疫原性细胞死亡，进一步提高免疫治疗的疗效。总之，基于SBV的治疗平台SBV@PDA/ICG（SBV@P/I）可以通过联合免疫疗法和光疗协同引发安全有效的肿瘤特异性抗肿瘤反应。