Neutrophil-based Trojan horse containing polymer nano-therapeutics for sono-activatable ferroptosis-immunotherapy of orthotopic glioma

被引：10

作者：

Ding, Mengbin ^{[1
]}

Zhu, Anni ^{[1
]}

Zhang, Yijing ^{[1
]}

Liu, Jiansheng ^{[1
]}

Lin, Lin ^{[2
]}

Wang, Xiaoying ^{[3
]}

Li, Jingchao ^{[1
]}

机构：

[1] Donghua Univ, Coll Biol Sci & Med Engn, State Key Lab Modificat Chem Fibers & Polymer Mat, Shanghai 201620, Peoples R China

[2] Fujian Med Univ, Dept Radiol, Union Hosp, Fuzhou 350001, Peoples R China

[3] Shanghai Jiao Tong Univ, Off Hosp Infect & Dis Control & Prevent, Shanghai Gen Hosp, Sch Med, Shanghai 200080, Peoples R China

来源：

NANO TODAY | 2024年 / 57卷

基金：

中国国家自然科学基金;

关键词：

Orthotopic glioma; Immunotherapy; Ferroptosis; Sono-activatable; Polymer nanoparticles; DELIVERY; NANOPARTICLES;

D O I：

10.1016/j.nantod.2024.102398

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The blood-brain barrier (BBB) and tumor microenvironment of glioma limit the efficacies of various therapies, and thus glioma treatment is challenging. We herein report semiconducting polymer nano-therapeutics (SPCFe/ siP) that can achieve efficient delivery into orthotopic glioma sites via neutrophil-mediated BBB transport for sono-activatable ferroptosis-immunotherapy. Such SPCFe/siP contain a semiconducting polymer, programmed death-ligand 1 (PD-L1) siRNA and iron oxide (Fe3O4) nanoparticles loaded into a singlet oxygen (1O2)-cleavable nanocarrier with surface conjugation of a neutrophil targeting ligand, sialic acid. SPCFe/siP effectively bind to neutrophils via sialic acid-based targeting pathway, and neutrophils containing SPCFe/siP serve as Trojan horses to migrate across BBB for improved delivery efficacy into orthotopic glioma sites. Upon irradiation by ultrasound (US), the semiconducting polymers produce 1O2 to destroy 1O2-cleavable nanocarriers for precise on-demand releases of Fe3O4 nanoparticles and PD-L1 siRNA, in which, Fe3O4 nanoparticles induce ferroptosis and subsequent immunogenic cell death (ICD), and PD-L1 siRNA downregulated the expression of PD-L1 for tumor cells, allowing for sono-activatable ferroptosis-immunotherapy. A strong immunological effect is formed, leading to noteworthy restriction of orthotopic glioma tumor growth and improvement of mouse survival. This study provides a neutrophil-targeting nanosystem with efficient brain delivery and activatable therapeutic action for treatment of orthotopic glioma.

引用

页数：16