CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exploring Morphology of Thermoplasmonic Nanoparticles to Synergize Immunotherapeutic Fibroblast Activation Protein-Positive Cell Sensitization and Photothermal Therapy.
Exploring Morphology of Thermoplasmonic Nanoparticles to Synergize Immunotherapeutic Fibroblast Activation Protein-Positive Cell Sensitization and Photothermal Therapy.
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光热治疗(PTT)的精准性常常受限于如何实现热等离子体纳米结构对肿瘤的选择性递送。主动靶向利用合成分子复合物识别恶性细胞过表达的受体,从而实现这种特异性,并促进PTT与其他抗癌疗法的联合应用。
在本研究中,我们开发了热等离子体纳米偶联物,其由以下两部分组成:(i)20 nm球形金纳米颗粒(AuNPs)或金纳米星(AuNSs)作为纳米载体,以及(ii)表面钝化的基于抗体的成纤维细胞活化蛋白(FAP)靶向模块,该模块用于适应性CAR-T 细胞免疫治疗。荧光激活细胞分选、免疫荧光和表面等离子体共振散射成像证实,该纳米偶联物具有优异的稳定性,并能特异性结合表达FAP的纤维肉瘤HT1080——该细胞经基因修饰以表达人FAP。
此外,该纳米载体在可见光和近红外照射后表现出显著的光热转换。定量热透镜光谱表明,AuNSs具有更优异的光热能力,在相同条件下其热增强效果最高可达AuNPs的1.5倍。这种将靶向免疫治疗与热等离子体纳米载体相结合的协同策略,不仅简化了纳米颗粒递送、提高了光热产率和治疗效果,还为癌症治疗提供了一种全面而强效的策略,并具有在多种治疗模式中取得更优结局的潜力。
The precision of photothermal therapy (PTT) is often hindered by the challenge of achieving selective delivery of thermoplasmonic nanostructures to tumors. Active targeting, which leverages synthetic molecular complexes to address receptors overexpressed by malignant cells, enables such specificity and facilitates the combination of the PTT with other anticancer therapies.
In this study, we developed thermoplasmonic nanoconjugates consisting of (i) 20 nm spherical gold nanoparticles (AuNPs) or gold nanostars (AuNSs) as nanocarriers, and (ii) surface-passivated antibody-based fibroblast activation protein (FAP)-targeting modules, used in adaptive chimeric antigen receptor T-cells immunotherapy.
The nanoconjugates demonstrated excellent stability and specific binding to FAP-expressing fibrosarcoma HT1080 genetically modified to express human FAP, as confirmed by fluorescence activated cell sorting, immunofluorescence, and surface plasmon resonance scattering imaging.
Moreover, the nanocarriers showed significant photothermal conversion after visible and near-infrared irradiation. Quantitative thermal lens spectroscopy demonstrated the superior photothermal capability of AuNSs, achieving up to 1. 5-fold greater thermal enhancement than AuNPs under identical conditions.
This synergistic approach, combining targeted immunotherapy with the thermoplasmonic nanocarriers, not only streamlines nanoparticle delivery, increasing photothermal yield and therapeutic efficacy but also offers a comprehensive and potent strategy for cancer treatment with the potential for superior outcomes across multiple modalities.
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