Bacteria-assisted delivery and oxygen production of nano-enzyme for potent radioimmunotherapy of cancer
Bacteria-assisted delivery and oxygen production of nano-enzyme for potent radioimmunotherapy of cancer
复制标题
细菌辅助纳米酶的输送和氧气产生，用于癌症的有效放射免疫治疗
DOI：
10.1007/s12274-022-4369-4
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发表时间：
2022-05-17
期刊：
影响因子：
9.9
通讯作者：
Yang, Kai
中科院分区：
文献类型：
--
作者：
Ni, Jing;Zhou, Hailin;Yang, Kai
肿瘤靶向减毒沙门氏菌可通过其增殖特性和随之产生的激活免疫应答诱导一定的抗肿瘤治疗作用，而以中性粒细胞为代表的宿主防御细胞则通过在细菌感染的肿瘤中产生过量的过氧化氢（H2 O2）-包括活性氧来捕获和清除这些入侵细菌，从而削弱细菌治疗肿瘤的疗效。因此，我们尝试将联合收割机细菌治疗与氧依赖性放射免疫治疗相结合，通过将纳米过氧化氢酶注射到细菌治疗的小鼠体内，获得理想的肿瘤治疗效果。变性白蛋白用于包被过氧化氢酶，并将其递送到细菌感染的肿瘤组织中浸润的中性粒细胞。利用中性粒细胞产生H2 O2，在纳米酶的催化下产生易扩散的氧气并扩散到整个肿瘤，从而增强缺氧肿瘤细胞的放射治疗。此外，优化的肿瘤微环境，由细菌的有效免疫刺激，产生氧气和肿瘤放疗协同引起，将增强抗肿瘤免疫力。这种新的联合治疗策略具有很大的希望，为未来的临床癌症治疗提供新的思路。
Tumor-targeting attenuated Salmonella could induce certain antitumor therapeutic effect through its proliferation characteristic and the consequent activated immune response, while host defense cells represented by neutrophils would trap and eliminate these invading bacteria via producing excess hydrogen peroxide (H2O2)-including reactive oxygen species in the bacteria-infected tumor, thereby impairing the efficacy of the bacteria treatment of tumor. Herein, we attempt to combine bacteria treatment and oxygen-dependent radioimmunotherapy of tumor through injection of neutrophil-targeted nano-catalase into the bacteria-treated mice for perfect tumor treatment outcome. Denatured albumin is used to coat catalase and deliver it to the neutrophils infiltrated in bacteria-infected tumor tissue. Taking advantage of the generating H2O2 by neutrophils, easily-diffused oxygen is produced and spread the whole tumor under the catalysis of nano-enzyme, leading to enhanced radiotherapy of hypoxic tumor cells. Moreover, the optimized tumor microenvironment, synergistically caused by potent immune-stimulation of bacteria, generating oxygen and tumor radiotherapy, would boost the antitumor immunity. This novel combination therapy strategy holds great promise to provide new ideas for future clinical cancer treatment.