Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Chemistry and Chemical Engineering , Linyi University , Linyi 276005 , P. R. China.
Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, College of Chemistry and Chemical Engineering, Qingdao University , Shandong 266071 , P. R. China.
Anal Chem. 2019 Jul 2;91(13):8549-8557. doi: 10.1021/acs.analchem.9b01805. Epub 2019 Jun 17.
Upconversion nanoparticles-based photodynamic nanotheranostic agents (UCNPs-PDT) have received great interest due to improved tissue penetration, weak autofluorescence, and low biotoxicity. However, conventional UCNPs-PDT are often limited by low energy transfer efficiency from UCNPs to photosensitizer (PS) molecules and insufficient generation and limited diffusion distance of reactive oxygen species (ROSs). Herein, an "all in one" nanotheranostic agent has been developed which has multicolor sandwich-structured UCNPs (SWUCNPs) as the core, a thin silica layer with a mitochondria-targeted group for loading dual PS as the medium layer, and polyethylene glycol-folic acid (PEG-FA) chains as the outer layer. Multicolor SWUCNPs simultaneously achieve two-photon fluorescence imaging and serve as energy donor for dual PS molecules. The thin luminescence layer and silica layer control most UCNPs activators and PS molecules in the effective energy transfer distance to guarantee a high energy transfer efficiency. Via FA-mediated endocytosis, the nanotheranostic agent is selectively endocytosed by cancer cells, is released from the endosome/lysosome, targets the mitochondria, and in situ produces ROSs under excitation from NIR, leading to significant mitochondria-mediated cell apoptosis. Furthermore, the established nanotheranostic agent shows tumor targetability, increased generation of ROSs, high PDT efficacy, significant cell apoptosis, minimal systemic cytotoxicity, and efficacious in vivo tumor inhibition.
上转换纳米粒子基光动力纳米诊疗剂（UCNPs-PDT）因其提高了组织穿透性、弱自发荧光和低生物毒性而受到广泛关注。然而，传统的 UCNPs-PDT 常常受到从 UCNPs 到光敏剂（PS）分子的能量转移效率低以及活性氧（ROS）的产生和扩散距离有限的限制。在此，开发了一种“一体化”纳米诊疗剂，它具有多色三明治结构的上转换纳米粒子（SWUCNPs）作为核心，薄的二氧化硅层带有靶向线粒体的基团用于装载双 PS 作为中间层，以及聚乙二醇-叶酸（PEG-FA）链作为外层。多色 SWUCNPs 同时实现了双光子荧光成像，并作为双 PS 分子的能量供体。薄的发光层和二氧化硅层将大多数 UCNPs 激活剂和 PS 分子控制在有效的能量转移距离内，以保证高的能量转移效率。通过 FA 介导的内吞作用，纳米诊疗剂被癌细胞选择性地内吞，从内体/溶酶体中释放出来，靶向线粒体，并在近红外光激发下原位产生 ROS，导致显著的线粒体介导的细胞凋亡。此外，所建立的纳米诊疗剂具有肿瘤靶向性、增加 ROS 的产生、高 PDT 疗效、显著的细胞凋亡、最小的全身细胞毒性和有效的体内肿瘤抑制作用。
