溶瘤病毒
上睑下垂
接种疫苗
Boosting(机器学习)
原位
生物正交化学
免疫
癌症研究
纳米技术
医学
病毒学
化学
材料科学
免疫系统
免疫学
计算机科学
组合化学
肿瘤细胞
炎症体
有机化学
机器学习
点击化学
炎症
作者
Xiaoyu Xu,Jinhua Zheng,Na Liang,Xu Zhang,Shayibai Shabiti,Zixi Wang,Yu Shibata,Pan Zhang,Wenjun Li,Lintao Cai
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-03-24
标识
DOI:10.1021/acsnano.3c11023
摘要
Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situ tumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situ tumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in "cold" tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situ tumor vaccines.
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