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A systematic assessment of hydroxyapatite nanoparticles used in the treatment of melanoma

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Abstract

Melanoma is a highly malignant skin tumor which is prone to recurrence and metastasis. Hydroxyapatite nanoparticles (nHAPs) were reported to possess a suppressive effect on proliferation of various tumor cells in vitro. This study aimed to assess in vitro and in vivo anti-tumor ability and biosafety of the nHAPs used in the treatment of melanoma. Three types of nHAPs with different morphology and crystallinity were synthesized. In vitro cell viability and proliferation studies demonstrated that all three types of nHAPs can inhibit viability and proliferation of A375 and SK-MEL-28 melanoma cells in a concentration-dependent manner. In addition, the rod-shape nHAPs with a crystallinity of 45.60% had the most prominent suppressive effect on the two melanoma cells tested. An important positive regulator of G1/S phase transition in cell cycle, Cyclin D1 protein, was reduced by nHAPs treatment in vivo. We further discovered that the migration ability of the nHAPs treated melanoma cells was greatly decreased. RNA sequencing result revealed that melanoma metastasis related genes were down-regulated by nHAPs, including MMP2, MMP14, ITGA9, ITGB3, ITGB4 and S100B. High concentration of nHAPs treatment in melanoma-bearing nude mice showed a strong inhibitory effect on tumor size and weight. Most importantly, hemolysis, electrolyte disturbance or inflammation response was not discovered in the experimental animals from nHAPs treated groups. We proved that the nHAPs synthesized in the current study has a selective effect to suppress melanoma tumor proliferation and was safe with regard to normal cells and tissue.

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Acknowledgements

This work was financially supported by National Key Research and Development Program of China (Nos. 2017YFB0702600 and 2017YFB0702604), Sichuan Science and Technology Innovation Team of China (No. 2019JDTD0008) and “111” Project of China (No. B16033).

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Authors and Affiliations

  1. Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Zhongtao Li, Jiaoqing Tang & Lin Wang

  2. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China

    Hongfeng Wu, Zhixin Ling, Siyu Chen, Xiao Yang, Xiangdong Zhu & Xingdong Zhang

  3. Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, 610041, China

    Yong Zhou & Chongqi Tu

  4. Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Bo Guo

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  1. Zhongtao Li
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Li, Z., Tang, J., Wu, H. et al. A systematic assessment of hydroxyapatite nanoparticles used in the treatment of melanoma. Nano Res. 13, 2106–2117 (2020). https://doi.org/10.1007/s12274-020-2817-6

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