Hydrogen-Peroxide-Responsive Protein Biomimetic Nanoparticles for Photothermal-Photodynamic Combination Therapy of Melanoma.

Abstract

Recently, there has been a rapid increase in the incidences of melanoma, which represents a serious threat to human health. Generally, tumor-microenvironment-responsive nanoparticle-based photothermal-photodynamic combination therapy (PTT-PDT) is characterized by intratumoral response and tumor targeting. In this study, we designed and synthesized hydrogen-peroxide-responsive protein biomimetic nanoparticles (MnO2 -ICG@BSA) for the treatment of melanoma. Briefly, MnO2 -ICG@BSA was prepared using a mild protein synthesis method by loading indocyanine green (ICG) into a bovine serum albumin-manganese dioxide complex (MnO2 @BSA); next, its characteristics were determined. In addition, in vitro biocompatibility and antitumor efficacy were assessed using the classic cell counting kit-8 assay. Moreover, in vivo high-frequency ultrasound and thermal imaging were used to evaluate the oxygen-production capacity and photothermal conversion effect of MnO2 -ICG@BSA at the tumor site, and Singlet Oxygen Sensor Green (SOSG) was used to measure singlet oxygen levels in the tumor. The antitumor efficacy was assessed based on relative tumor size, bodyweight, survival curves, and hematoxylin and eosin staining. The results showed that MnO2 -ICG@BSA has a high photothermal conversion efficiency, a strong singlet oxygen-generation ability, and high photothermal stability. In addition, in vitro PTT-PDT experiments showed that MnO2 -ICG@BSA has a significant inhibitory effect on the proliferation of B16F10 melanoma cells. Meanwhile, in vivo experiments showed that MnO2 -ICG@BSA has a significant inhibitory effect on melanoma in mice. Preliminary toxicity studies indicated that MnO2 -ICG@BSA exhibits low toxicity. From the results, we can conclude that MnO2 -ICG@BSA could be used in PTT-PDT to treat melanoma, making it a good candidate material for PTT-PDT. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.