Record-High Ultrasound-Sensitive NO Nanogenerators for Cascade Tumor Pyroptosis and Immunotherapy.
Record-High Ultrasound-Sensitive NO Nanogenerators for Cascade Tumor Pyroptosis and Immunotherapy.
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DOI：
10.1002/advs.202302278
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发表时间：
2023-09
期刊：
影响因子：
15.1
通讯作者：
Tong, Weijun
中科院分区：
文献类型：
--
作者：
Bao, Yuheng;Ge, Yanni;Wu, Mengjie;Mao, Zhengwei;Ye, Juan;Tong, Weijun
焦亡是一种促炎性细胞死亡，与针对肿瘤的先天免疫促进相关。过量的一氧化氮（NO）触发的氮应激有可能诱导细胞凋亡，但NO的精确递送具有挑战性。超声（US）响应NO的产生由于其深穿透性、低副作用、非侵入性和局部激活方式而具有主导优先权。本工作选择了具有生物活性的US敏感NO供体N-甲基-N-亚硝基苯胺（NMA），并将其负载到透明质酸（HA）修饰的中空二氧化锰纳米颗粒（hMnO 2 NPs）中，制备了hMnO2@HA@NMA（MHN）纳米发电机（NG）。所获得的NG在US照射下具有创纪录的高NO生成效率，并且在靶向肿瘤部位后可以释放Mn 2+。随后，实现了基于级联肿瘤细胞凋亡和干扰素基因的环GMP‐AMP合酶刺激因子（cGAS‐STING）的免疫治疗，并有效抑制了肿瘤生长。通过hMnO2@HA@NMA（MHN）纳米发电机（NG）在肿瘤部位进行级联肿瘤细胞凋亡和干扰素基因的环GMP-AMP合酶-刺激因子（cGAS-STING）免疫治疗。MHN NG在超声辐照下可产生一氧化氮（NO）并释放Mn ~（2+）。在由NO诱导的焦亡后，双链DNA从肿瘤细胞中释放，这有助于Mn 2+增强的cGAS-STING途径。
Pyroptosis is a pro‐inflammatory cell death that is associated with innate immunity promotion against tumors. Excess nitric oxide (NO)‐triggered nitric stress has potential to induce pyroptosis, but the precise delivery of NO is challenging. Ultrasound (US)‐responsive NO production has dominant priority due to its deep penetration, low side effects, noninvasion, and local activation manner. In this work, US‐sensitive NO donor N‐methyl‐N‐nitrosoaniline (NMA) with thermodynamically favorable structure is selected and loaded into hyaluronic acid (HA)‐modified hollow manganese dioxide nanoparticles (hMnO2 NPs) to fabricate hMnO2@HA@NMA (MHN) nanogenerators (NGs). The obtained NGs have a record‐high NO generation efficiency under US irradiation and can release Mn2+ after targeting the tumor sites. Later on, cascade tumor pyroptosis and cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING)‐based immunotherapy is achieved and tumor growth is effectively inhibited. Cascade tumor pyroptosis and cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) immunotherapy at tumor sites by hMnO2@HA@NMA (MHN) nanogenerators (NGs). MHN NGs can produce nitric oxide (NO) under ultrasound irradiation and release Mn2+ ion. After pyroptosis induced by NO, double‐stranded DNA is released from tumor cells, which contributes to Mn2+‐enhanced cGAS‐STING pathway.
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