Near-Infrared Light-Triggered Photodynamic Therapy and Apoptosis Using Upconversion Nanoparticles With Dual Photosensitizers.

Yong Il Park,Song Yeul Lee,Eunha Kim,Ruda Lee,Sanghee Lee

doi:10.3389/fbioe.2020.00275

Abstract

Elucidation of upconversion nanoparticles (UCNPs) that can be excited by near-infrared (NIR) light is an interesting topic in the field of photodynamic therapy (PDT). However, the PDT efficiency of conventional UCNPs is limited due to the low quantum yield and overheating effect of the 980 nm light source. In this study, a light source with a wavelength of 808 nm was used as an excitation source for Nd-doped UCNPs to solve the overheating effect. UCNPs with a core@shell structure (NaYF4:Yb,Er,Nd@NaYF4:Yb,Nd) were synthesized to increase the upconversion emission efficiency. Dual-color emitting Er-doped UCNPs and dual photosensitizers (Chlorin e6 and Rose Bengal) were used for enhanced PDT. Each photosensitizer could absorb red and green emissions of the UCNPs to generate reactive oxygen species (ROS), respectively. The ROS generation in a dual photosensitizer system is significantly higher than that in a single photosensitizer system. Additionally, PDT induces immunogenic apoptosis. In this study, by utilizing a highly efficient PDT agent, PDT-induced apoptosis was studied by biomarker analysis.

Highlights

Various anticancer therapies are currently being tested in clinics
To assess the cellular photodynamic therapy (PDT) effect, the cells with PS-upconversion nanoparticles (UCNPs) uptake were irradiated for 10 min using the 808 nm continuous wave (CW) laser (∼600 mW) and incubated for 24 h (Xu et al, 2017a; Ding et al, 2018)
To confirm the reactive oxygen species (ROS) generation, in vitro cellular studies were performed on the B16BL6 melanoma cells

Summary

INTRODUCTION

Various anticancer therapies are currently being tested in clinics. new cancer remedies are still needed for selective and efficient treatment with minimal side effects. For efficient photosensitizer activation using the 808 nm NIR wavelength excitation, NaYF4:Yb,Er,Nd@NaYF4:Yb,Nd was selected as Nd-doped UCNPs with a core@shell structure (Huang and Lin, 2015). 1 mL of the ABDA stock solution was added to 1 mg of UCNPs loaded with different photosensitizers, respectively. To assess the cellular PDT effect, the cells with PS-UCNP uptake were irradiated for 10 min using the 808 nm CW laser (∼600 mW) and incubated for 24 h (Xu et al, 2017a; Ding et al, 2018). The B16BL6 melanoma cells were seeded in a 96-well plate at a density of 5 × 103 cells per well and the UCNPs, RBUCNPs, Ce6-UCNPs, and RB/Ce6-UCNPs were incubated for 24 h, respectively. The ROS in the live cells were measured using the DCFDA/H2DCFDA assay kit according to the manufacturer’s instructions (Abcam). The one-way ANOVA test was used for the statistical analysis of significance, followed by a Tukey’s t-test. p-values of ∗∗∗ < 0.001 were considered statistically significant

RESULTS AND DISCUSSION

CONCLUSION

DATA AVAILABILITY STATEMENT