Wang Ruliang, Yang Han, Fu Rongxin, Su Ya, Lin Xue, Jin Xiangyu, Du Wenli, Shan Xiaohui, Huang Guoliang
Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
Cancers (Basel). 2020 Oct 27;12(11):3136. doi: 10.3390/cancers12113136.
Multimodal imaging-guided near-infrared (NIR) photothermal therapy (PTT) is an interesting and promising cancer theranostic method. However, most of the multimodal imaging systems provide structural and functional information used for imaging guidance separately by directly combining independent imaging systems with different detectors, and many problems arise when trying to fuse different modal images that are serially taken by inviting extra markers or image fusion algorithms. Further, most imaging and therapeutic agents passively target tumors through the enhanced permeability and retention (EPR) effect, which leads to low utilization efficiency. To address these problems and systematically improve the performance of the imaging-guided PTT methodology, we report a novel simultaneous dual-modal imaging system combined with cancer cell membrane-coated nanoparticles as a platform for PTT-based cancer theranostics. A novel detector with the ability to detect both high-energy X-ray and low-energy visible light at the same time, as well as a dual-modal imaging system based on the detector, was developed for simultaneous dual-modal imaging. Cancer cell membrane-coated upconversion nanoparticles (CC-UCNPs) and gold nanoparticles (CC-AuNPs) with the capacity for immune evasion and active tumor targeting were engineered for highly specific imaging and high-efficiency PTT therapy. In vitro and in vivo evaluation of macrophage escape and active homologous tumor targeting were performed. Cancer cell membrane-coated nanoparticles (CC-NPs) displayed excellent immune evasion ability, longer blood circulation time, and higher tumor targeting specificity compared to normal PEGylated nanoparticles, which led to highly specific upconversion luminescence (UCL) imaging and PTT-based anti-tumor efficacy. The anti-cancer efficacy of the dual-modal imaging-guided PTT was also evaluated both in vitro and in vivo. Dual-modal imaging yielded precise anatomical and functional information for the PTT process, and complete tumor ablation was achieved with CC-AuNPs. Our biomimetic UCNP/AuNP and novel simultaneous dual-modal imaging combination could be a promising platform and methodology for cancer theranostics.
多模态成像引导的近红外（NIR）光热疗法（PTT）是一种有趣且有前景的癌症诊疗方法。然而，大多数多模态成像系统通过直接将独立成像系统与不同探测器组合，分别提供用于成像引导的结构和功能信息，并且在尝试融合通过引入额外标记物或图像融合算法串行获取的不同模态图像时会出现许多问题。此外，大多数成像和治疗剂通过增强的渗透和滞留（EPR）效应被动靶向肿瘤，这导致利用效率低下。为了解决这些问题并系统地提高成像引导的PTT方法的性能，我们报告了一种新型的同步双模态成像系统，该系统结合了癌细胞膜包被的纳米颗粒，作为基于PTT的癌症诊疗平台。开发了一种能够同时检测高能X射线和低能可见光的新型探测器，以及基于该探测器的双模态成像系统，用于同步双模态成像。设计了具有免疫逃逸和主动肿瘤靶向能力的癌细胞膜包被的上转换纳米颗粒（CC-UCNPs）和金纳米颗粒（CC-AuNPs），用于高特异性成像和高效PTT治疗。进行了巨噬细胞逃逸和主动同源肿瘤靶向的体外和体内评估。与正常聚乙二醇化纳米颗粒相比，癌细胞膜包被的纳米颗粒（CC-NPs）表现出优异的免疫逃逸能力、更长的血液循环时间和更高的肿瘤靶向特异性，这导致了高特异性的上转换发光（UCL）成像和基于PTT的抗肿瘤疗效。还在体外和体内评估了双模态成像引导的PTT的抗癌疗效。双模态成像为PTT过程提供了精确的解剖和功能信息，并且使用CC-AuNPs实现了完全的肿瘤消融。我们的仿生UCNP/AuNP和新型同步双模态成像组合可能是一种有前景的癌症诊疗平台和方法。
