Chen Huachao, Bi Qirui, Yao Yongrong, Tan Ninghua
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
J Mater Chem B. 2018 Jul 14;6(26):4351-4359. doi: 10.1039/c8tb00665b. Epub 2018 Jun 21.
This work reports a dimeric BODIPY (BDP)-loaded liposome with conjugation of anti-HIF antibodies for dual hypoxia marker imaging and nitroreductase (NTR)-activatable photodynamic therapy (PDT) against hypoxic tumors. In this theranostic nanosystem (designated Ab-DiBDP NPs), the newly designed orthogonal BDP dimer has high O quantum yield, and the substitution of a nitro group at the meso-position leads to the NTR-controllable activation of phototoxicity and fluorescence. Both in vivo and in vitro experiments demonstrate that the NTR-activatable PDT liposome can efficiently destroy cancer cells and prevent damage to normal cells. More significantly, the fascinating advantage of the nanoprobe is the synergy between the Cy 7-marked anti-HIF-1α antibody and the NTR-activatable DiBDP, which significantly improves the accuracy of tumor hypoxia imaging by simultaneous detection of NTR and HIF-1α. Therefore, this work presents a new paradigm for NTR-triggered PDT against cancer cells and provides a new avenue for precise tumor hypoxia diagnosis.
这项工作报道了一种负载二聚体BODIPY（BDP）的脂质体，其与抗缺氧诱导因子（HIF）抗体偶联，用于双缺氧标志物成像以及针对缺氧肿瘤的硝基还原酶（NTR）激活的光动力疗法（PDT）。在这种诊疗纳米系统（命名为Ab-DiBDP NPs）中，新设计的正交BDP二聚体具有高的单线态氧量子产率，并且在中位位置取代硝基导致光毒性和荧光的NTR可控激活。体内和体外实验均表明，NTR激活的PDT脂质体能够有效破坏癌细胞并防止对正常细胞的损伤。更重要的是，该纳米探针的迷人优势在于Cy 7标记的抗HIF-1α抗体与NTR激活的DiBDP之间的协同作用，通过同时检测NTR和HIF-1α，显著提高了肿瘤缺氧成像的准确性。因此，这项工作为NTR触发的针对癌细胞的PDT提出了一种新的范例，并为精确的肿瘤缺氧诊断提供了一条新途径。
