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Theranostics 2020; 10(11):4720-4736. doi:10.7150/thno.43092 This issue Cite

Research Paper

Bioactive phospho-therapy with black phosphorus for in vivo tumor suppression

Shengyong Geng^1,2, Ting Pan¹, Wenhua Zhou¹, Haodong Cui¹, Lie Wu¹, Zhibin Li¹, Paul K. Chu³, Xue-Feng Yu^1,4✉

1. Materials and Interfaces Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
2. Medical Oncology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518055, China
3. Department of Physics, Department of Materials Science and Engineering, and Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China
4. Institute of Environment and Health, Jianghan University, Wuhan 430056, China

✉ Corresponding author: Xue-Feng Yu, Tel: +86-13971313505, Email: xf.yuac.cn

Abstract

Background and Purpose: Although inorganic nanomaterials have been widely used in multimodal cancer therapies, the intrinsic contributions of the materials are not well understood and sometimes underestimated. In this work, bioactive phospho-therapy with black phosphorus nanosheets (BPs) for in vivo tumor suppression is studied.

Methods: Orthotopic liver tumor and acute myeloid leukemia are chosen as the models for the solid tumor and hematological tumor, respectively. BPs are injected into mice through the tail vein and tumor growth is monitored by IVIS bioluminescence imaging. Tumor tissues and serum samples are collected to determine the suppression effect and biosafety of BPs after treatment.

Results: The in vitro studies show that BPs with high intracellular uptake produce apoptosis- and autophagy-mediated programmed cell death of human liver carcinoma cells but do not affect normal cells. BPs passively accumulate in the tumor site at a high concentration and inhibit tumor growth. The tumor weight is much less than that observed from the doxorubicin (DOX)-treated group. The average survival time is extended by at least two months and the survival rate is 100% after 120 days. Western bolt analysis confirms that BPs suppress carcinoma growth via the apoptosis and autophagy pathways. In addition, administration of BPs into mice suffering from leukemia results in tumor suppression and long survival.

Conclusions: This study reveals that BPs constitute a type of bioactive anti-cancer agents and provides insights into the application of inorganic nanomaterials to cancer therapy.

Keywords: black phosphorus, bioactive phospho-therapy, selective cell killing, two-dimensional nanomaterials, cancer therapy

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