A hemoglobin-based oxygen-carrying biomimetic nanosystem for enhanced chemo-phototherapy and hypoxia alleviation of hepatocellular carcinoma

Tumor microenvironment is characterized by low pH, high reactive oxygen species and hypoxia, which provides a suitable environment for cancer growth. The hypoxia not only elevates tumor angiogenesis and metastasis, but also is responsible for the development of treatment resistance, which gradually becomes a significant impediment for cancer therapy. Therefore, we developed a biomimetic nanosystem containing hemoglobin extracted from red blood cells, chemotherapy drug sorafenib, sensitizer ursolic acid and photosensitizer indocyanine green for enhanced chemo-photo combination therapy of hepato-cellular carcinoma, which could not only enhance the chemotherapy effect of sorafenib bowing to the sensitizing effect of ursolic acid, but also achieved synergetic phototherapy in virtue of indocyanine green. Besides, the nanoparticles could effectively delivery exogenous oxygen to tumor site and amelio-rate the tumor hypoxic environment with the assistance of hemoglobin. The dual-sensitization drug delivery system was expected to effectively reduce the resistance of traditional treatment methods against tumor hypoxia, providing a novel prospect for the synergistic hepatocellular carcinoma treatment.(c) 2023 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.

Automated summary

The tumor microenvironment has low pH, high ROS levels, and hypoxia, which facilitate cancer growth. Hypoxia not only promotes tumor angiogenesis and metastasis, but also leads to treatment resistance, which hinders cancer therapy. In this study, a biomimetic nanosystem containing red blood cell-derived hemoglobin, chemotherapy drug sorafenib, sensitizer ursolic acid, and photosensitizer indocyanine green was developed for enhanced chemo-phototherapy of hepatocellular carcinoma. The nanosystem improves chemotherapy efficacy through synergistic effects of ursolic acid and achieves phototherapy using indocyanine green. Additionally, hemoglobin facilitates oxygen delivery to the tumor site and ameliorates the hypoxic environment. This dual-sensitization drug delivery system shows promise in overcoming treatment resistance caused by tumor hypoxia in hepatocellular carcinoma.