胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤之一，但其诊断和治疗仍然是一个巨大的挑战。在此，报道了中性粒细胞靶向半导体聚合物纳米治疗剂（SSPNiNO）用于小鼠模型中原位胶质母细胞瘤的第二次近红外（NIR-II）荧光成像引导三模式治疗。 SSPNiNO是基于两种半导体聚合物形成的，分别充当NIR-II荧光探针和光热转换剂。热响应性一氧化氮 (NO) 供体和腺苷 2A 受体 (A2AR) 抑制剂共同整合到 SSPNiNO 中，以实现三模式治疗作用。 SSPNiNO 表面附着有中性粒细胞靶向配体，可通过“特洛伊木马”方式介导其有效递送至原位 GBM 位点，从而实现高灵敏度 NIR-II 荧光成像。在NIR-II光照射下，SSPNiNO通过NIR-II光热效应有效产生热量，不仅杀死肿瘤细胞并诱导免疫原性细胞死亡（ICD），而且还触发受控的NO释放以强化肿瘤ICD。此外，封装的A2AR抑制剂可以通过阻断腺苷-A2AR通路来调节免疫抑制性肿瘤微环境，从而进一步增强抗肿瘤免疫作用，从而显着抑制原位GBM进展。这项研究可以为 NIR-II 荧光成像引导的有效 GBM 治疗提供具有累积治疗作用的多功能治疗诊断纳米平台。© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

Glioblastoma (GBM) is one of the deadliest primary brain tumors, but its diagnosis and curative therapy still remain a big challenge. Herein, neutrophil-targeting semiconducting polymer nanotheranostics (SSPNiNO) is reported for second near-infrared (NIR-II) fluorescence imaging-guided trimodal therapy of orthotopic glioblastoma in mouse models. The SSPNiNO are formed based on two semiconducting polymers acting as NIR-II fluorescence probe as well as photothermal conversion agent, respectively. A thermal-responsive nitric oxide (NO) donor and an adenosine 2A receptor (A2AR) inhibitor are co-integrated into SSPNiNO to enable trimodal therapeutic actions. SSPNiNO are surface attached with a neutrophil-targeting ligand to mediate their effective delivery into orthotopic GBM sites via a "Trojan Horse" manner, enabling high-sensitive NIR-II fluorescence imaging. Upon NIR-II light illumination, SSPNiNO effectively generates heat via NIR-II photothermal effect, which not only kills tumor cells and induces immunogenic cell death (ICD), but also triggers controlled NO release to strengthen tumor ICD. Additionally, the encapsulated A2AR inhibitor can modulate immunosuppressive tumor microenvironment by blocking adenosine-A2AR pathway, which further boosts the antitumor immunological effect to observably suppress the orthotopic GBM progression. This study can provide a multifunctional theranostic nanoplatform with cumulative therapeutic actions for NIR-II fluorescence imaging-guided effective GBM treatment.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.