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

abstract

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).

keywords

DRUG-DELIVERY; DNA INTERACTION; CANCER-THERAPY; IN-VIVO; COMPLEXES; NANOPARTICLES; ACID; CHEMISTRY; REAGENTS; MELANOMA

subject category

Biochemistry & Molecular Biology; Chemistry

authors

Batten, MR; Gutiérrez-Orgaz, JA; Maturi, FE; Carlos, LD; Oliveira, H; Hernando, J; Novio, F; Rodríguez-Diéguez, A; Capdevila, M; Palacios, O; Bayón, P

our authors

acknowledgements

Financial support was provided by the Spanish Ministerio de Ciencia e Innovacion through the project: PID2022-138479NB-I00. M. C., O. P., and P. B. are members of the "Grups de Recerca"-Generalitat de Catalunya, ref. 2021SGR00668. J. H. thanks Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR)-Generalitat de Catalunya for its support through the project ref. 2021SGR00064. F. N. thanks MICIU/AEI/10 .13039/501100011033 and European Union Next Generation EU/PRTR for their support with grant CNS2022-136106. F. N. also thanks MCIU/AEI/10.13039/501100011033/and ERDF for grant PID2021-127983OB-C21. F. E. M., L. D. C., and H. O. thank the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020) and CESAM (UIDP/50017/2020 and UIDB/50017/2020 and LA/P/0094/2020) , financed by national funds through the FCT/MCTES (PIDDAC) . This work was also supported by the project PTDC/BTM-MAT/31794/2017 (POCI-01-0145-FEDER-031794) , funded by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) -and by national funds (OE) , through FCT/MCTES.

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