Riboflavin photoactivation by upconversion nanoparticles for cancer treatment
Abstract
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