Nanosonosensitizer-Augmented Sono-Immunotherapy for Glioblastoma by Non-Invasive Opening of the Blood-Brain Barrier

Danmin Lin; Zhen Wang; Wei LongMingze XuAolu LiuYifei GaoZhu WenChao LiuJiecheng HeYuxue ChengSiyuan JiangJiapeng ChenQingpeng LiuLingkun ZhangRong YouLiang YinYanqing Guan

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Nanosonosensitizer-Augmented Sono-Immunotherapy for Glioblastoma by Non-Invasive Opening of the Blood-Brain Barrier

机译：Nanosonosensitizer-Augmented Sono-Immunotherapy for Glioblastoma by Non-Invasive Opening of the Blood-Brain Barrier

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The presence of blood-brain barrier (BBB) that limits effective penetration oftherapeutics is the main reason for poor outcomes of glioblastoma (GBM)treatment. Ultrasound (US) combined with microbubbles (MBs) can preciselydisrupt the tight junctions of brain endothelial cells, thus creating “acousticpores” and non-invasive opening the BBB. Here, chitosan oligosaccharide(COS) is conjugated with a sonosensitizer protoporphyrin IX (PpIX) and animmune-enhancing adjuvant Poly(I:C) via electrostatic adsorption, and crosslinkedwith a tumor-targeting molecule hyaluronic acid (HA) affording nanosonosensitizersHA-Poly(I:C)/COS-PpIX (abbreviated as “HP/CP” NSs). HP/CP NSs can target and penetrate GBMs, and trigger reactive oxygen speciesproduction upon US, simultaneously causing mitochondrial dysfunction andDNA damage. Tumor-associated antigens released by sonodynamic therapyinducedimmunogenic cell death and loaded Poly(I:C) form an in situ vaccinetogether to potentiate antitumor immune responses. In orthotopic GBMmice models, the HP/CP+US treatments prolong mice survival, enhancecytotoxic T-lymphocytes infiltration, and activate peripheral immune circulation.Besides, HP/CP NSs possess favorable biosafety profiles. Collectively,this study sheds light on the application of HP/CP NSs for synergistic sonoimmunotherapyof GBMs after non-invasive opening of the BBB.

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来源
《Advanced functional materials》 |2023年第6期|2209219.1-2209219.13|共13页
作者
Danmin Lin; Zhen Wang; Wei LongMingze XuAolu LiuYifei GaoZhu WenChao LiuJiecheng HeYuxue ChengSiyuan JiangJiapeng ChenQingpeng LiuLingkun ZhangRong YouLiang YinYanqing Guan;
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School of Life Science South China Normal University Guangzhou 510631, China;

School of Biomedical and Pharmaceutical Sciences Guangdong University of Technology Guangzhou 510006, China;

School of Life Science South China Normal University Guangzhou 510631, China,South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central Hospital Guangzhou 511400, ChinaSchool of Life Science South China Normal University Guangzhou 510631, China,South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central Hospital Guangzhou 511400, China,Guangzhou Key Laboratory of;

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apoptosis; blood-brain barrier; glioblastoma; nanosonosensitizers; sono-immunotherapy;

Nanosonosensitizer-Augmented Sono-Immunotherapy for Glioblastoma by Non-Invasive Opening of the Blood-Brain Barrier

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