Meng Hong-Min, Lu Limin, Zhao Xu-Hua, Chen Zhuo, Zhao Zilong, Yang Chan, Zhang Xiao-Bing, Tan Weihong
†Molecular Sciences and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, China.
‡College of Science, Jiangxi Agricultural University, Nanchang 330045, China.
Anal Chem. 2015 Apr 21;87(8):4448-54. doi: 10.1021/acs.analchem.5b00337. Epub 2015 Mar 31.
Many one-photon fluorescence-based theranostic nanosystems have been developed for simultaneous therapeutic intervention/monitoring for various types of cancers. However, for early diagnosis of cancer, two-photon fluorescence microscopy (TPFM) can realize deep-tissue imaging with higher spatial resolution. In this study, we first report a multiple functional nanoprobe for contrast-enhanced bimodal cellular imaging and targeted therapy. Components of the nanoprobe include (1) two-photon dye-doped mesoporous silica nanoparticles (TPD-MSNs); (2) MnO2 nanosheets that act as a (i) gatekeeper for TPD-MSNs, (ii) quencher for TP fluorescence, and (iii) contrast agent for MRI; (3) cancer cell-targeting aptamers. Guided by aptamers, TPD-MSNs are rapidly internalized into the target cells. Next, intracellular glutathione reduces MnO2 to Mn(2+) ions, resulting in contrast-enhanced TP fluorescence and magnetic resonance signal for cellular imaging. Meanwhile, preloaded doxorubicin and Chlorin e6 are released for chemotherapy and photodynamic therapy, respectively, with a synergistic effect and significantly enhanced therapeutic efficacy.
许多基于单光子荧光的诊疗纳米系统已被开发用于对各种类型癌症进行同步治疗干预/监测。然而，对于癌症的早期诊断，双光子荧光显微镜（TPFM）能够实现具有更高空间分辨率的深层组织成像。在本研究中，我们首次报道了一种用于对比增强双峰细胞成像和靶向治疗的多功能纳米探针。该纳米探针的组成部分包括：（1）双光子染料掺杂的介孔二氧化硅纳米颗粒（TPD-MSNs）；（2）二氧化锰纳米片，其充当（i）TPD-MSNs的守门人，（ii）TP荧光的猝灭剂，以及（iii）MRI的造影剂；（3）癌细胞靶向适体。在适体的引导下，TPD-MSNs迅速内化进入靶细胞。接下来，细胞内的谷胱甘肽将二氧化锰还原为锰离子，从而产生用于细胞成像的对比增强TP荧光和磁共振信号。同时，预加载的阿霉素和二氢卟吩e6分别释放用于化疗和光动力治疗，具有协同效应且显著提高治疗效果。
