Wang Yiru, Wu Ming, Wang Xiaorong, Wang Peiyuan, Ning Zhaoyu, Zeng Yongyi, Liu Xiaolong, Sun Haiyan, Zheng Aixian
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, PR China.
College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China.
Mater Today Bio. 2022 Dec 28;18:100531. doi: 10.1016/j.mtbio.2022.100531. eCollection 2023 Feb.
Immune checkpoint blockade (ICB) is emerging as a promising therapeutic approach for clinical treatment against various cancers. However, ICB based monotherapies still suffer from low immune response rate due to the limited and exhausted tumor-infiltrating lymphocytes as well as tumor immunosuppressive microenvironment. In this work, the cell membrane with surface displaying PD-1 proteins (PD1-CM) was prepared for immune checkpoint blockade, which was further combined with multifunctional and biodegradable MnO for systematic and robust antitumor therapy. The MnO-based gene-engineered nanocomposites can catalyze the decomposition of abundant HO in TME to generate O, which can promote the intratumoral infiltration of T cells, and thus improve the effect of immune checkpoint blockade by PD-1 proteins on PD1-CM. Furthermore, MnO in the nanocomposites can be completely degraded into Mn, which can catalyze the generation of highly toxic hydroxyl radicals for chemodynamic therapy, thereby further enhancing the therapeutic effect. In addition, the prepared nanocomposites possess the advantages of low cost, easy preparation and good biocompatibility, which are expected to become promising agents for combination immunotherapy.
免疫检查点阻断(ICB)正在成为一种针对各种癌症进行临床治疗的有前景的治疗方法。然而,由于肿瘤浸润淋巴细胞数量有限且耗竭,以及肿瘤免疫抑制微环境,基于ICB的单一疗法的免疫反应率仍然较低。在这项工作中,制备了表面展示PD-1蛋白的细胞膜(PD1-CM)用于免疫检查点阻断,并将其与多功能可生物降解的MnO相结合,用于系统且强大的抗肿瘤治疗。基于MnO的基因工程纳米复合材料可以催化肿瘤微环境(TME)中大量的H₂O₂分解产生O₂,这可以促进T细胞在肿瘤内浸润,从而提高PD-1蛋白在PD1-CM上的免疫检查点阻断效果。此外,纳米复合材料中的MnO可以完全降解为Mn²⁺,其可以催化产生高毒性的羟基自由基用于化学动力学治疗,从而进一步增强治疗效果。此外,所制备的纳米复合材料具有成本低、易于制备和良好生物相容性的优点,有望成为联合免疫治疗的有前景的药物。
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