Riboflavin photoactivation by upconversion nanoparticles for cancer treatment

E.V. Khaydukov (1) , K.E. Mironova (1, 2) , V.A. Semchishen (1) , A.N. Generalova (1, 2) , A.V. Nechaev (1, 3) , D.A. Khochenkov (1) , E.V. Stepanova (4) , O.I. Lebedev (5) , A.V. Zvyagin (1, 6) , S.M. Deyev (2) , V.Ya. Panchenko (1)

1 FRC - Federal Research Center Krasnoyarsk Scientific Center
2 IBCh RAS - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
3 MSTU Stankin - Moscow State Technological University
4 N.N. Blokhin Russian Cancer Research Center
5 CRISMAT - Laboratoire de cristallographie et sciences des matériaux
6 Macquarie University

Riboflavin (Rf) is a vitamin and endogenous photosensitizer capable to generate reactive oxygen species (ROS) under UV-blue irradiation and kill cancer cells, which are characterized by the enhanced uptake of Rf. We confirmed its phototoxicity on human breast adenocarcinoma cells SK-BR-3 preincubated with 30-μM Rf and irradiated with ultraviolet light, and proved that such Rf concentrations (60 μM) are attainable in vivo in tumour site by systemic intravascular injection. In order to extend the Rf photosensitization depth in cancer tissue to 6 mm in depth, we purpose-designed core/shell upconversion nanoparticles (UCNPs, NaYF4Yb3+Tm3+/NaYF4) capable to convert 2% of the deeply-penetrating excitation at 975 nm to ultraviolet-blue power. This power was expended to photosensitise Rf and kill SK-BR-3 cells preincubated with UCNPs and Rf, where the UCNP-Rf energy transfer was photon-mediated with ∼14% Förster process contribution. SK-BR-3 xenograft regression in mice was observed for 50 days, following the Rf-UCNPs peritumoural injection and near-infrared light photodynamic treatment of the lesions. © 2016 The Author(s).

Keywords: Animal; Breast tumor; C57BL mouse; Chemistry; CHO cell line; Cricetulus; DBA mouse; Drug effects; Drug screening; Experimental neoplasm; Human; Lewis carcinoma; Metabolism; Mouse; Pathology; Procedures; Tumor cell line; Animals; Breast Neoplasms; Carcinoma; Lewis Lung; Cell Line; Tumor; Cell Survival; CHO Cells; Female; Fluorides; Humans; Metal Nanoparticles; Mice; Inbred C57BL; Inbred DBA; Neoplasms; Experimental; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Riboflavin; Thulium; Xenograft Model Antitumor Assays; Ytterbium; Yttrium; Biophotonics; Drug development; Fluoride; Metal nanoparticle; Photosensitizing agent; Reactive oxygen metabolite; Sodium yttriumtetrafluoride

Domains: Chemical Sciences; Chemical Sciences; Cristallography; Chemical Sciences; Theoretical and/or physical chemistry; Chemical Sciences; Material chemistry

E.V. Khaydukov, K.E. Mironova, V.A. Semchishen, A.N. Generalova, A.V. Nechaev, et al.. Riboflavin photoactivation by upconversion nanoparticles for cancer treatment. Scientific Reports, 2016, 6, pp.35103. ⟨10.1038/srep35103⟩. ⟨hal-02184755⟩