Dual-Action Pt(IV) Prodrugs and Targeted Delivery in Metal-Organic Frameworks: Overcoming Cisplatin Resistance and Improving Anticancer Activity

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Abstract
The conversion of cisplatin Pt(II) into a Pt(IV) complex is a strategy that can be used to overcome cisplatin resistance and side effects, and this involves the functionalization of the axial positions of cisplatin. Using ligands with bioactivity to target specific cancer cell species could lead to targeted treatment and mitigate severe side effects. Furthermore, enhanced cellular uptake could be used to overcome cisplatin resistance. Anchoring the “dual-acting” prodrug in self-assembled hybrid porous metal-organic frameworks (MOFs) has revealed an even more advanced treatment. The exceptional porosity allows high loading of the drug, and the easily tuned functional groups within the frameworks enable various interactions between the drug and the cargo material to optimize controlled release and prevent premature release. Some MOFs have also demonstrated cytotoxicity against several cancer lines. It is expected that the combination of the prodrug and active MOFs could generate a “triple-acting” anticancer agent for more enhanced cancer treatment. This review discusses the development of cisplatin modified with several prodrugs and its anticancer activity in several cancer cell lines. Furthermore, the review summarizes the involvement of cisplatin derivatives in MOFs, highlighting the slow, controlled, and targeted delivery of the drug and its anticancer activity.

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