Liu Lingjun, Zhang Junya, An Ruibing, Xue Qi, Cheng Xi, Hu Yuxuan, Huang Zheng, Wu Luyan, Zeng Wenhui, Miao Yinxing, Li Jie, Zhou Yu, Chen Hong-Yuan, Liu Hong, Ye Deju
State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.
Angew Chem Int Ed Engl. 2023 Mar 1;62(10):e202217055. doi: 10.1002/anie.202217055. Epub 2023 Jan 31.
Tumor-targeted and stimuli-activatable nanosensitizers are highly desirable for cancer theranostics. However, designing smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumor-targeted and redox-activatable nanosensitizers (1-NPs) for sono-photodynamic immunotherapy of tumors by molecular co-assembly and redox-controlled disassembly. 1-NPs show a high longitudinal relaxivity (r =18.7±0.3 mM s ), but "off" dual fluorescence (FL) emission (at 547 and 672 nm), "off" sono-photodynamic therapy and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1-NPs rapidly disassemble and remotely release small molecules 2-Gd, Zn-PPA-SH and NLG919, concurrently switching on (1) dual FL emission, (2) sono-photodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1-NPs are effective for bimodal FL and magnetic resonance (MR) imaging-guided sono-photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671-nm laser irradiation.
肿瘤靶向且可刺激激活的纳米敏化剂在癌症诊疗中极具吸引力。然而，设计具有多种成像信号且能开启协同治疗活性的智能纳米敏化剂具有挑战性。在此，我们报道了通过分子共组装和氧化还原控制解离制备的用于肿瘤声动力免疫治疗的肿瘤靶向且氧化还原可激活的纳米敏化剂（1-NPs）。1-NPs具有高纵向弛豫率（r =18.7±0.3 mM⁻¹ s⁻¹），但双荧光（FL）发射“关闭”（在547和672 nm处）、声动力治疗“关闭”以及吲哚胺2,3-双加氧酶1（IDO1）抑制活性“关闭”。经谷胱甘肽（GSH）还原后，1-NPs迅速解离并远程释放小分子2-Gd、Zn-PPA-SH和NLG919，同时开启（1）双FL发射、（2）声动力治疗和（3）IDO1抑制活性。全身注射后，在联合超声（US）和671-nm激光照射下，1-NPs对小鼠原位乳腺肿瘤和脑肿瘤的双模态FL和磁共振（MR）成像引导的声动力免疫治疗有效。
