免疫疗法
材料科学
血脑屏障
免疫原性细胞死亡
纳米载体
光热治疗
透明质酸
癌症研究
医学
免疫学
免疫系统
纳米技术
中枢神经系统
药物输送
解剖
内分泌学
作者
Danmin Lin,Zhen Wang,Wei Long,Mingze Xu,Aolu Liu,Yifei Gao,Wen Zhu,Chao Liu,Jiecheng He,Yuxue Cheng,Siyuan Jiang,Jiapeng Chen,Qingpeng Liu,Lingkun Zhang,Rong You,Liang Yin,Yan‐Qing Guan
标识
DOI:10.1002/adfm.202209219
摘要
Abstract The presence of blood–brain barrier (BBB) that limits effective penetration of therapeutics is the main reason for poor outcomes of glioblastoma (GBM) treatment. Ultrasound (US) combined with microbubbles (MBs) can precisely disrupt the tight junctions of brain endothelial cells, thus creating “acoustic pores” and non‐invasive opening the BBB. Here, chitosan oligosaccharide (COS) is conjugated with a sonosensitizer protoporphyrin IX (PpIX) and an immune‐enhancing adjuvant Poly(I:C) via electrostatic adsorption, and cross‐linked with a tumor‐targeting molecule hyaluronic acid (HA) affording nanosonosensitizers HA‐Poly(I:C)/COS‐PpIX (abbreviated as “HP/CP” NSs). HP/CP NSs can target and penetrate GBMs, and trigger reactive oxygen species production upon US, simultaneously causing mitochondrial dysfunction and DNA damage. Tumor‐associated antigens released by sonodynamic therapy‐induced immunogenic cell death and loaded Poly(I:C) form an in situ vaccine together to potentiate antitumor immune responses. In orthotopic GBM mice models, the HP/CP+US treatments prolong mice survival, enhance cytotoxic 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 sono‐immunotherapy of GBMs after non‐invasive opening of the BBB.
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