An intelligent core-shell microneedle patch loaded with oxygen-vacancy-engineered ROS nanogenerators for a programmed ICB therapy against "cold" tumors

被引：0

作者：

Li, Yang ^{[1
,2
,3
]}

Zhang, Zixuan ^{[1
,2
,3
]}

Zhao, Wei ^{[1
,2
,3
]}

Li, Haijie ^{[1
,2
,3
]}

Fu, Rongzhan ^{[1
,2
,3
]}

Li, Jiachen ^{[4
]}

Fan, Daidi ^{[1
,2
,3
]}

机构：

[1] Northwest Univ, Engn Res Ctr Western Resource Innovat Med Green Mf, Sch Chem Engn, Minist Educ, Xian 710127, Peoples R China

[2] Northwest Univ, Shaanxi R&D Ctr Biomat & Fermentat Engn, Sch Chem Engn, Shaanxi Key Lab Biomat & Synthet Biol, Xian 710127, Peoples R China

[3] Northwest Univ, Biotech & Biomed Res Inst, Xian 710127, Peoples R China

[4] Northwest Univ, Sch Chem Engn, Xian Key Lab Special Energy Mat, Xian 710127, Peoples R China

来源：

CHEMICAL ENGINEERING JOURNAL | 2025年 / 507卷

基金：

中国国家自然科学基金;

关键词：

Intelligent-responsive; Core-shell microneedle; Oxygen vacancy engineering; Cold" tumor; NANOPARTICLES; FABRICATION;

D O I：

10.1016/j.cej.2025.160621

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Reactive oxygen species (ROS)-enhanced immune checkpoint blockade (ICB) therapy holds great promise for treating "cold" tumors. However, protecting ICB antibodies from ROS-induced damage and achieving a spatiotemporally controlled programmed immunotherapy remain significant challenges. Herein, an intelligentresponsive core-shell microneedle patch is developed to deliver oxygen-vacancy-engineered ROS nanogenerators and ICB antibodies in a programmed manner for augmented ICB efficacy against "cold" tumors. The fast-dissolving microneedle shell is loaded with MRuGH ROS nanogenerators, which are constructed by decorating oxygen-vacancy-engineered MXene@RuO2 heterojunctions with hemoglobin and glucose oxidase. Meanwhile, the ROS-responsive microneedle core delivers aPD-1 ICB antibodies, which are encapsulated in glutathione (GSH)-sensitive silica nanospheres (SP NSs). In the tumor microenvironment (TME), MRuGH releases quickly from the microneedle shell, further responds hypoxic TME to release oxygen and then produces efficient ROS through glucose-activated cascade reaction and ultrasound stimulation-mediated sonodynamic therapy. The generated ROS can reshape immunosuppressive "cold" tumors into immunostimulated "hot" tumors and then induce the degradation of microneedle core due to the cleavage of borate-ester bonds. Sequentially, SP NSs are released from the core and further respond over-expressed GSH to deliver aPD-1 for ICB therapy. This approach protects the antibodies from ROS-induced damage and achieves a spatiotemporally controlled programmed immunotherapy, thereby significantly suppressing the tumor growth and offering a promising programmed ICB therapy for "cold" tumors.

引用

页数：17