Near-infrared activation of upconversion platforms for non-redox-dependent release of Pt(II)

Upconversion nanoparticles (UCNPs) are a class of interesting nanomaterials with unique multi-photon excitation photoluminescence properties, and they have been intensively explored as novel contrast agents for biomedical imaging and drug delivery. The development of photoinduced drug-release devices has been intensively developed in the last years, specially using UCNPs due to their properties to absorb single-band near infrared (NIR) light and subsequently emit high-energy UV-to-visible light which could photoactivate several prodrugs. Some examples of Pt(II) release have been described, all of them from Pt(IV) complexes taking advantage of the Pt(IV)/(II) redox couple. In this work, NIR light-responsive LiYF₄:Yb/Tm UCNPs are presented as carrier systems to exert photoinduced Pt(II) drug release. For this, the surface of UCNPs were coated with an amphiphilic polymer to convert hydrophobic nanoparticles into hydrophilic and to load novel Pt(II) complexes. It is demonstrated that NIR radiation-induced Pt(II) drug release can be achieved without the need to use the Pt(IV)/(II) redox couple as a trigger. In this way, under NIR excitation, UCNPs can transform NIR irradiation into UV radiation which causes direct Pt(II) drug release in a spatial and temporal control manner. The release process has been monitored in real-time. Two platforms containing two different Pt(II) complexes have been studied, both showing similar results in terms of the enhancement of toxicity caused by the increase in Pt(II) concentration. Furthermore, a significant improvement of cytotoxicity against melanoma A375 cells was observed after irradiation of these platforms, confirming the feasibility of the proposed upconversion process to release Pt(II).