Hybrid system {W6I8}-cluster/dsDNA as an agent for targeted X-ray induced photodynamic therapy of cancer stem cells†
Abstract
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.