NaYF4:Yb3+/Er3+ Upconversion Nanoparticles for Infrared Photodynamic Therapy of Tumors

Abstract

Luminescence spectra of oleylamine- (OM) cubic or pure hexagonal OM-NaYF4:Yb3+/Er3+ nanoparticles demonstrated that these light-upconverting nanoparticles produced upconversion luminescence at ∼670 nm under excitation at 980 nm. When coupled with a photosensitizer (phthalocyanine), the resulting drug formulation was suitable for infra-red photodynamic therapy (PDT) of tumors (1) as proven by pre-clinical testing with xeno-transplanted human tumors to athymic nude (nu/nu) mice. Laser 980 nm irradiation penetrating deeper into the skin and tissue did not cure xenotransplanted tumors in nude mice i.v. injected with photosenzitizer-free nanoparticles, whereas tumor remissions frequently occurred after i.v. injected phthalocyanine-contaning light-upconverting nanoparticles. Prior to photosensitizer incorporation, the OM-NaYF4:Yb3+/Er3+ nanoparticles were coated by a silica shell to enable further amino-functionalization and render the particles with biocompatibility and stability in aqueous media, preventing particles from aggregation. By varying the reaction time and Ln3+/Na+/F- ratio, the nanocrystal size was controlled within the range 16-270 nm (2). In vitro cytotoxicity and intracellular nanoparticle uptake were determined with human cervix carcinoma mRoGFP HeLa cells using confocal microscopy. In conclusion, infra-red PDT was established.Supported from GACR (15-01897S) and Czech Ministry of Education (LF14001).(1) Nekvasil, M., Zadinova, M., Tahotna, L., Žackova, M., Pouckova, P., Ježek, P. An optimum modality for photodynamic therapy of tumors: gels containing liposomes with hydrophobic photosenzitizers. Drug. Dev. Res. 68, 235-252, 2007.(2) Kostiv U, Janouskova O, Slouf M, Kotov N, Engstova H, Smolkova K, Ježek P, Horak, D. Silica-modified monodisperse hexagonal lanthanide nanocrystals: Synthesis and biological properties Nanoscale, 2015.