Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China; The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang Province, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China.
Biomaterials. 2022 Sep;288:121711. doi: 10.1016/j.biomaterials.2022.121711. Epub 2022 Aug 5.
The tumor immune microenvironment (TIME) is one of the significant hallmarks of cancer and has the important role of largely determining the malignancy level of tumors. As an approach to break through this bottleneck of tumor treatment methods, the TIME can be reprogrammed by certain nanomaterials. Here, we coated C-novyi-spores with melittin-RADA nanofiber hybrid peptide and loaded the immunomodulator metformin to obtain MRM-coated spores as a powerful antitumor nanodrug against glioblastoma (GBM), which is based on the activation of the TIME. MRM-coated spores exhibit extended-release profiles and an enhanced killing effect on GBM both in vitro and in vivo. Furthermore, MRM-coated spores can educate the innate and adaptive immune system by inducing sustainable CD8 T cell responses, promoting M1 macrophage polarization, and regulating the expression of HIF1-α, PDL1, and CXCL9 in TIME. In intracranial applications, MRM-coated spores showed excellent biosafety and a strong therapeutic effect. In summary, peptide hydrogels provide a promising strategy in which advantages of different treatment methods can be incorporated to synthesize potent antitumor drugs with mild side effects from bacteria-mediated nanomaterials.
肿瘤免疫微环境（TIME）是癌症的重要特征之一，在很大程度上决定了肿瘤的恶性程度。作为突破肿瘤治疗方法这一瓶颈的一种方法，可以通过某些纳米材料对 TIME 进行重新编程。在这里，我们用蜂毒素-RADA 纳米纤维杂合肽包被 C-诺维芽孢杆菌孢子，并负载免疫调节剂二甲双胍，以获得基于激活 TIME 的强大抗脑胶质瘤（GBM）纳米药物-MRM 包被孢子。MRM 包被孢子表现出延长的释放曲线，并在体外和体内均增强了对 GBM 的杀伤作用。此外，MRM 包被孢子可通过诱导持续的 CD8 T 细胞反应、促进 M1 巨噬细胞极化以及调节 TIME 中的 HIF1-α、PDL1 和 CXCL9 的表达来教育先天和适应性免疫系统。在颅内应用中，MRM 包被孢子表现出优异的生物安全性和强大的治疗效果。总之，肽水凝胶提供了一种很有前途的策略，其中可以结合不同治疗方法的优势，从细菌介导的纳米材料中合成具有温和副作用的强效抗肿瘤药物。
