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多色荧光成像指导下近红外二区的可编程化疗和免疫治疗乳腺癌。

Programmable Chemotherapy and Immunotherapy against Breast Cancer Guided by Multiplexed Fluorescence Imaging in the Second Near-Infrared Window.

机构信息

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine and i-Lab, CAS Center for Excellence in Brain Science, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

出版信息

Adv Mater. 2018 Dec;30(51):e1804437. doi: 10.1002/adma.201804437. Epub 2018 Oct 25.

Abstract

Combined chemotherapy and immunotherapy have demonstrated great potential in cancer treatment. However, it is difficult to provide clear information of the pharmacokinetics and pharmacodynamics of chemodrugs and transplanted immune cells in vivo by traditional approaches, resulting in inadequate therapy. Here, a multiplexed intravital imaging strategy by using fluorescence in the second near-infrared window (NIR-II) is first developed to visualize the two events of chemotherapy and immunotherapy in vivo, so that a combinational administration is programed to improve the therapeutical effects against a mouse model of human breast cancer. In detail, Ag Se quantum dots (QDs) (λ = 1350 nm) loaded with stromal-cell-derived factor-1α (SDF-1α) and chemodrug doxorubicin (DOX) are first administrated to deliver the SDF-1α and DOX to the tumor site. After their arrival, monitored by Ag Se QD fluorescence, natural killer (NK)-92 cells labeled with Ag S QDs (λ = 1050 nm) are intravenously injected so that the cells are recruited to the tumor by the chemotaxis of SDF-1α, which is visualized by Ag S QD fluorescence. Such an imaging approach allows simultaneous evaluation of the behaviors of individual injections in vivo, and facilitates optimized administration regimens, resulting in enhanced tumor inhibition.

摘要

联合化疗和免疫疗法在癌症治疗中显示出巨大的潜力。然而,传统方法很难提供体内化疗药物和移植免疫细胞的药代动力学和药效学的明确信息,导致治疗不足。在这里,首次开发了一种基于近红外二区(NIR-II)荧光的多重活体成像策略,用于可视化体内的化疗和免疫治疗这两个事件,从而编程联合给药以提高针对人乳腺癌小鼠模型的治疗效果。具体而言,负载基质细胞衍生因子-1α(SDF-1α)和化疗药物阿霉素(DOX)的 Ag Se 量子点(QD)(λ = 1350nm)首先被给予,将 SDF-1α 和 DOX 递送至肿瘤部位。到达后,Ag Se QD 荧光监测下,静脉注射标记有 Ag S QD(λ = 1050nm)的自然杀伤(NK)-92 细胞,通过 SDF-1α 的趋化作用将细胞募集到肿瘤部位,Ag S QD 荧光可对其进行可视化。这种成像方法可以同时评估体内单个注射的行为,并有助于优化给药方案,从而增强肿瘤抑制。

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