一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
英文原题:Temperature-Feedback Nanoplatform for NIR-II Penta-Modal Imaging-Guided Synergistic Photothermal Therapy and CAR-NK Immunotherapy of Lung Cancer.
Temperature-Feedback Nanoplatform for NIR-II Penta-Modal Imaging-Guided Synergistic Photothermal Therapy and CAR-NK Immunotherapy of Lung Cancer.
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本研究旨在协同实施光热治疗(PTT)和肿瘤靶向免疫治疗的同时,直观获取肺癌全面的结构与功能信息,因此构建了一种诊疗一体化纳米平台 UCILA:将上转换纳米颗粒(UCNP)和 IR-1048 染料引入脂质-适配体纳米结构。嵌入脂质双层的 IR-1048 染料可在第二近红外(NIR-II)窗口用于光声成像、光学相干断层扫描血管成像、光热成像及 PTT。UCILA 内部负载的 UCNP 具有优异发光性能和较高 X 射线衰减系数,可作为计算机断层扫描(CT)和温度敏感上转换发光(UCL)成像造影剂,实现肿瘤代谢活动实时追踪及温度反馈式 PTT。在五模态成像辅助和 PTT 期间精准监测局部温度变化的基础上,UCILA 能有效消融肺肿瘤且副作用极小。
同时实施协同 CAR-NK 免疫治疗,特异性清除 PTT 后可能残留的肿瘤细胞。因此,UCILA 纳米平台被证明是一种多功能诊疗剂,可用于五模态成像和温度反馈式 PTT,并同步开展肺癌靶向免疫治疗。
In this study, to visually acquire all-round structural and functional information of lung cancer while performing synergistic photothermal therapy (PTT) and tumor-targeting immunotherapy, a theranostic nanoplatform that introduced upconversion nanoparticles (UCNPs) and IR-1048 dye into the lipid-aptamer nanostructrure (UCILA) is constructed.
Interestingly, the IR-1048 dye grafted into the lipid bilayer can serve as the theranostic agent for photoacoustic imaging, optical coherence tomography angiography, photothermal imaging, and PTT in the second near infrared (NIR-II) window.
In addition, loaded in the inner part of UCILA, UCNPs possess the superior luminescence property and high X-ray attenuation coefficient, which can act as contrast agents for computed tomography (CT) and thermo-sensitive up-conversion luminescence (UCL) imaging, enabling real-time tracking of metabolic activity of tumor and temperature-feedback PTT.
Furthermore, under the complementary guidance of penta-modal imaging and an accurate monitoring of in situ temperature change during PTT, UCILA exhibits its excellent capability for ablating the lung tumor with minimal side effects. Meanwhile, synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT.
Therefore, the UCILA nanoplatform is demonstrated as a multifunctional theranostic agent for both penta-modal imaging and temperature-feedback PTT while conducting targeting immunotherapy of lung cancer.
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