Quental Letícia, Raposinho Paula, Mendes Filipa, Santos Isabel, Navarro-Ranninger Carmen, Alvarez-Valdes Amparo, Huang Huaiyi, Chao Hui, Rubbiani Riccardo, Gasser Gilles, Quiroga Adoración G, Paulo António
Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal.
Dalton Trans. 2017 Oct 31;46(42):14523-14536. doi: 10.1039/c7dt00043j.
In this article, we report on the development of new metal-based anticancer agents with imaging, chemotherapeutic and photosensitizing properties. Hence, a new heterobimetallic complex (Pt-LQ-Re) was prepared by connecting a non-conventional trans-chlorido Pt(ii) complex to a photoactive Re tricarbonyl unit (LQ-Re), which can be replaced by Tc to allow for in vivo imaging. We describe the photophysical and biological properties of the new complexes, in the dark and upon light irradiation (DNA interaction, cellular localization and uptake, and cytotoxicity). Furthermore, planar scintigraphic images of mice injected with Pt-LQ-Tc clearly showed that the radioactive compound is taken up by the excretory system organs, namely liver and kidneys, without significant retention in other tissues. All in all, the strategy of conjugating a chemotherapeutic compound with a PDT photosensitizer endows the resulting complexes with an intrinsic cytotoxic activity in the dark, driven by the non-classical platinum core, and a selective activity upon light irradiation. Most importantly, the possibility of integrating a SPECT imaging radiometal (Tc) in the structure of these new heterobimetallic complexes might allow for in vivo non-invasive visualization of their tumoral accumulation, a crucial issue to predict therapeutic outcomes.
在本文中，我们报道了具有成像、化疗和光敏特性的新型金属基抗癌剂的研发情况。因此，通过将一种非常规的反式氯铂（II）配合物与一个光活性铼三羰基单元（LQ-Re）相连，制备了一种新的异双金属配合物（Pt-LQ-Re），该单元可用锝取代以实现体内成像。我们描述了新配合物在黑暗中和光照下的光物理和生物学特性（DNA相互作用、细胞定位与摄取以及细胞毒性）。此外，注射了Pt-LQ-Tc的小鼠的平面闪烁图像清楚地表明，放射性化合物被排泄系统器官，即肝脏和肾脏摄取，在其他组织中无明显滞留。总而言之，将化疗化合物与光动力疗法（PDT）光敏剂结合的策略赋予了所得配合物在黑暗中由非经典铂核心驱动的内在细胞毒性活性，以及光照后的选择性活性。最重要的是，在这些新的异双金属配合物结构中整合单光子发射计算机断层扫描（SPECT）成像放射性金属（锝）的可能性可能允许对其肿瘤积累进行体内非侵入性可视化，这是预测治疗结果的关键问题。
