844 Upconversion composite nanoparticles modulate melanoma oxidative stress and enhance NIR-mediated photodynamic therapy

When treating superficial skin cancer, photodynamic therapy (PDT) provides improved spatiotemporal accuracy and minimal invasiveness compared to traditional therapies. However, due to the low penetration of visible (VIS) light and high reactive oxygen species (ROS) levels in cancer cells, melanoma can be resistant to PDT. To improve the efficacy of PDT in treating melanoma, we have prepared upconversion nanoparticles loaded with chlorin e6 (Ce6) and buthionine sulphoximine (BSO). The multifunctional UCNP-Ce6-BSO (UCB) nanoparticles can utilize near-infrared (NIR) light, thus enhancing their tissue penetration significantly. In addition, the UCB nanoparticles can modulate ROS levels by inhibiting glutamate-cysteine ligase. We have conducted both in vivo and in vitro studies. The UCB nanoparticles or control particles were injected intratumorally into B16-F10 bearing mice, a mouse melanoma model, before either near-infrared (NIR) or VIS irradiation. NIR irradiation resulted in obvious shrinkages of the tumors which remained small for 14 days. The average tumor size of the NIR-irradiated group was one tenth of the VIS-irradiated group. After NIR irradiation, the average tumor size of the UCB-treated group was one third (p<0.05) of the UCNP-Ce6 treated group. In order to evaluate the antitumor immune effects, tumor-infiltrating cells were purified. The amount of CD45+ lymphocytes and CD8+ CD107+ killer T cells in the UCB + NIR group were much higher than the control groups (p<0.05). Furthermore, our in vitro results showed that both the cell apoptosis levels and the released ROS levels increased significantly for the UCB + NIR group. In summary, our UCB nanoparticles offer enhanced tissue penetration and oxidative stress modulation, which present a unique PDT strategy for melanoma.