载乳酸氧化酶纳米粒通过耗竭乳酸调控免疫抑制微环境抑制肿瘤  

Lactate Depletion by Lactate Oxidase Loaded Nanoparticles for Tumor Immunosuppression Microenvironment Regulation and Tumor Suppression

作　　者：谭妍迪 黄菊 唐心一 张春美 向宏伟 李锐 Tan Yandi;Huang Ju;Tang Xinyi;Zhang Chunmei;Xiang Hongwei;Li Rui(Department of Ultrasound,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 40o030,China)

机构地区：[1]重庆医科大学附属第三医院超声科,重庆市400030

出　　处：《中国超声医学杂志》2022年第10期1183-1186,共4页Chinese Journal of Ultrasound in Medicine

基　　金：重庆市英才计划项目[No.渝委人才(2019)4号];重庆市基础研究与前沿探索专项(No.20190107);重庆医科大学附属第三医院科研孵化项目(No.KY08025)。

摘　　要：目的 探讨载乳酸氧化酶的中空介孔有机硅纳米粒(HMON-LOD)通过消耗肿瘤微环境中的乳酸改善免疫抑制微环境而抑制肿瘤作用。方法 制备HMON-LOD并检测其形态、粒径,包封率及氧化乳酸生成过氧化氢的催化作用。对CT26皮下移植瘤小鼠治疗后通过流式细胞数术检测肿瘤中T细胞及巨噬细胞的数量。通过抑瘤率、HE、TUNEL和PCNA染色观察治疗效果。结果 HMON-LOD为粒径均一的壳核结构,可有效将乳酸氧化酶装载在壳的表面,包封率为16.92%±2.35%。HMON-LOD可有效氧化乳酸生成过氧化氢,增加肿瘤中CT4~+T细胞、CT8~+T细胞的含量,促M2型巨噬细胞极化为M1型巨噬细胞,从而逆转肿瘤免疫抑制微环境、促肿瘤细胞凋亡抑肿瘤细胞增殖,最终抑制肿瘤的生长。结论 成功制备HMON-LOD,其可通过耗竭肿瘤微环境中的乳酸而缓解免疫抑制微环境,从而杀伤肿瘤。Objective To investigate the effect of immunosuppressive tumor microenvironment mitigation and tumor suppression by depletion of lactate in tumor microenvironment with the treatment of HMON-LOD. Methods HMON-LOD was prepared and its morphology, average size, and the encapsulation efficiency were detected. The catalytic activity of HMON-LOD was measured by the consumption of lactate and Oas well as the generation of HO. After treatments, the number of T cells and tumor-associated macrophages(TAMs) in CT26 xenograft mice tumor were detected by FCM. The tumor inhibition rate, H&E, TUNEL,and PCNA staining were performed to observe anti-tumor effect. Results HMON-LOD was homogeneously shell-core structured and carried LOD in the shell. The encapsulation efficiency was 16.92%±2.35%. HMON-LOD could effectively oxidase lactate and generate HO, increased the proportion of CD4and CD8T cells as well as polarized M2 TAMs to M1 TAMs. HMON-LOD reversed immunosuppressive tumor microenvironment, increased tumor apoptosis and inhibited tumor proliferation. HMON-LOD showed the effective antitumor activity. Conclusions HMON-LOD was successfully prepared and could efficiently consume the lactate in tumor microenvironment, resulting in tumor immunosuppression microenvironment regulation and tumor suppression.

关 键 词：中空介孔有机硅纳米粒 乳酸 肿瘤免疫抑制微环境 肿瘤 乳酸氧化酶 

分 类 号：R730.5[医药卫生—肿瘤]