Neutrophil‐Targeting Semiconducting Polymer Nanotheranostics for NIR‐II Fluorescence Imaging‐Guided Photothermal‐NO‐Immunotherapy of Orthotopic Glioblastoma

• Published in: Advanced science 2024-10, Vol.11 (39), p.e2406750-n/a
• Main Authors: Liu, Jiansheng, Cheng, Danling, Zhu, Anni, Ding, Mengbin, Yu, Ningyue, Li, Jingchao
• Format: Article
• Language: English
• Subjects: Brain cancer; cancer theranostics; Chemotherapy; fluorescence imaging; Genotype & phenotype; glioblastoma; Glioma; Immunotherapy; Lasers; Ligands; Medical prognosis; Nanoparticles; Neutrophils; Polymers; semiconducting polymer; Temperature; Tumors
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202406750

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. Neutrophil‐targeting semiconducting polymer nanotheranostics are designed for second near‐infrared fluorescence imaging‐guided combination therapy of orthotopic glioblastoma. The nanotheranostics can cross blood‐brain barrier and accumulate in tumor sites via hijacking neutrophils, which enables heat generation via photothermal effect to release nitric oxide and adenosine 2A receptor inhibitor to modulate tumor microenvironment. The nanotheranostics thus enable imaging‐guided photothermal‐NO‐immunotherapy to treat orthotopic glioblastoma.