Hybrid system {W6I8}-cluster/dsDNA as an agent for targeted X-ray induced photodynamic therapy of cancer stem cells,Materials Chemistry Frontiers

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Hybrid system {W6I8}-cluster/dsDNA as an agent for targeted X-ray induced photodynamic therapy of cancer stem cells
Materials Chemistry Frontiers ( IF 6.0 ) Pub Date : 2021-08-11 , DOI: 10.1039/d1qm00956g
Tatiana N. Pozmogova _{1,

2,

3} , Natalya A. Sitnikova ₁ , Ekaterina V. Pronina ₃ , Svetlana M. Miroshnichenko _{1,

4} , Andrey O. Kushnarenko ₁ , Anastasiya O. Solovieva ₁ , Sergey S. Bogachev ₅ , Georgy D. Vavilov ₆ , Olga A. Efremova ₁ , Yuri A. Vorotnikov ₃ , Michael A. Shestopalov ₃

Affiliation

Metastasis is one of the leading causes of the recurrence and high mortality of cancer. According to a recent hierarchical model of tumour formation, cancer stem cells (CSCs) are responsible for the occurrence of metastases and cancer relapse. Unfortunately, these cells are believed to have high resistance to conventional treatments. The development of therapies focused on the targeted elimination of cancer stem cells is now viewed as a new and advantageous approach to cancer treatment. Here we present a new material – a hybrid of double-stranded DNA (dsDNA) and hexatungsten iodide octahedral cluster {W₆I₈}⁴⁺ – as an effective agent for the targeted X-ray induced photodynamic therapy (X-PDT) of cancer stem cells. Specifically, our approach was to employ an intrinsic property of CSCs to selectively internalise dsDNA molecules to drag {W₆I₈}, scintillating and photosensitising moieties, directly into CSCs. The hybrid material has high stability in aqueous media, low cytotoxicity in the absence of irradiation, and significant selective cellular uptake by CSCs. X-Ray irradiation of CSCs incubated with the material resulted in an extremely low growth rate of the solid tumour in model CBA mice.

中文翻译：

混合系统 {W6I8}-cluster/dsDNA 作为靶向 X 射线诱导的癌症干细胞光动力治疗的试剂

转移是癌症复发和高死亡率的主要原因之一。根据最近的肿瘤形成分层模型，癌症干细胞 (CSC) 是转移和癌症复发的原因。不幸的是，这些细胞被认为对常规治疗具有很高的抵抗力。专注于靶向消除癌症干细胞的疗法的开发现在被视为一种新的、有利的癌症治疗方法。在这里，我们提出了一种新材料——双链 DNA (dsDNA) 和碘化_六钨八面体簇 {W ₆ I ₈ } ^{4+ 的}混合物– 作为癌症干细胞靶向 X 射线诱导光动力疗法 (X-PDT) 的有效药剂。具体来说，我们的方法是利用 CSC 的内在特性来选择性地内化 dsDNA 分子，从而将闪烁和光敏部分{W ₆ I ₈ } 直接拖入 CSC。该杂化材料在水性介质中具有高稳定性，在没有辐射的情况下具有低细胞毒性，并且 CSC 具有显着的选择性细胞摄取。与材料一起孵育的 CSC 的 X 射线照射导致模型 CBA 小鼠中实体瘤的生长速率极低。

更新日期：2021-09-01

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