Abstract
Polyoxometalates (POMs) are an emerging class of inorganic metal oxides, which over the last decades demonstrated promising biological activities by the virtue of their great diversity in structures and properties. They possess high potential for the inhibition of various tumor types; however, their unspecific interactions with biomolecules and toxicity impede their clinical usage. The current focus of the field of biologically active POMs lies on organically functionalized and POM‐based nanocomposite structures as these hybrids show enhanced anticancer activity and significantly reduced toxicity towards normal cells in comparison to unmodified POMs. Although the antitumor activity of POMs is well documented, their mechanisms of action are still not well understood. In this Review, an overview is given of the cytotoxic effects of POMs with a special focus on POM‐based hybrid and nanocomposite structures. Furthermore, we aim to provide proposed mode of actions and to identify molecular targets. POMs are expected to develop into the next generation of anticancer drugs that selectively target cancer cells while sparing healthy cells.
Highlights
Polyoxometalates (POMs) are an emerging class of inorganic metal From the Contents oxides, which over the last decades demonstrated promising biological activities by the virtue of their great diversity in structures and prop- 1
PM-8 was highly efficient in vivo by suppressing the tumor growth in Cancer is a malignant disease in which abnormal cells different mice models being partially more active than divide in an uncontrolled way, leading to the formation of approved drugs such as 5-fluorouracil (5-FU) and nimusa solid mass referred to as tumor or to blood cancers.[1] tine.[16]
All of them suffer from major disadvantages such as severe side effects owing to lack a mechanism for the anticancer activity of PM-8 which involves its reduction to PM-17 and its re-oxidation in which course the tumor cells are reduced and killed.[19]
Summary
After the auspicious results from PM-8 and other polyoxomolybdates (POMos; Supporting Information, Table S1), interest in this type of compounds peaked, leading to a vast number of biologically active POMs (Supporting Information, Tables S1–S3). The ZnII containing Krebs-POM was the most selective and clinically most suitable compound.[33] The MnII[34] and CoII[35] containing Krebs structures were tested on other cancer cell lines performing partially better than clinically approved drugs and were shown to induce apoptosis (Supporting Information, Table S2) Another POM inducing apoptosis is the CuII containing double Keggin POT (Figure 1 g) K7Na3[Cu4(H2O)2(PW9O34)2], which showed inhibitory effects against both human (MG-63) and rat (UMR-106) bone osteosarcoma (IC50 = 22 and 81 mm).[36] The POM increased the intracellular level of reactive oxygen species (ROS) while reducing that of. All of the reported inorganic POMs exhibiting antiproliferative activity are summarized in the Supporting Information, Tables S1–S3
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