State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, No. 1 Bei-Er-Tiao, Beijing, 100190, P. R. China.
School of Chemical Engineering, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, P. R. China.
Adv Mater. 2020 Nov;32(47):e2002085. doi: 10.1002/adma.202002085. Epub 2020 Oct 5.
The highly immunosuppressive tumor microenvironment (TME) in solid tumors often dampens the efficacy of immunotherapy. In this study, bacterial outer membrane vesicles (OMVs) are demonstrated as powerful immunostimulants for TME reprogramming. To overcome the obstacles of antibody-dependent clearance and high toxicity induced by OMVs upon intravenous injection (a classic clinically relevant delivery mode), calcium phosphate (CaP) shells are employed to cover the surface of OMVs, which enables potent OMV-based TME reprograming without side effects. Meanwhile, the pH-sensitive CaP shells facilitate the neutralization of acidic TME, leading to highly beneficial M2-to-M1 polarization of macrophages for improved antitumor effect. Moreover, the outer shells can be integrated with functional components like folic acid or photosensitizer agents, which facilitates the use of the OMV-based platform in combination therapies for a synergic therapeutic effect.
在实体瘤中，高度免疫抑制的肿瘤微环境（TME）常常削弱了免疫疗法的疗效。在这项研究中，细菌外膜囊泡（OMV）被证明是一种强大的免疫刺激物，可以对 TME 进行重新编程。为了克服抗体依赖性清除和 OMV 经静脉注射（一种经典的临床相关给药方式）引起的高毒性的障碍，采用磷酸钙（CaP）壳来覆盖 OMV 的表面，这使得基于 OMV 的 TME 重新编程具有强大的功效而没有副作用。同时，pH 敏感的 CaP 壳有利于中和酸性 TME，导致巨噬细胞发生有益的 M2 到 M1 极化，从而提高抗肿瘤效果。此外，外壳可以与功能成分（如叶酸或光敏剂）整合，这有利于基于 OMV 的平台在联合治疗中的应用，以达到协同的治疗效果。
