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Research Article

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

Zhongtao Li1, Jiaoqing Tang1, Hongfeng Wu2, Zhixin Ling2, Siyu Chen2, Yong Zhou3, Bo Guo4, Xiao Yang2( ), Xiangdong Zhu2, Lin Wang1( ), Chongqi Tu3, Xingdong Zhang2
Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu 610041, China
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu 610041, China
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China
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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.

Keywords

hydroxyapatite nanoparticlesmelanomaRNA sequencingmigrationbiosafety

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Nano Research
Volume 13 Issue 8,
August 2020
Pages 2106-2117
DOI: 10.1007/s12274-020-2817-6
Cite this article:
Li Z, Tang J, Wu H, et al. A systematic assessment of hydroxyapatite nanoparticles used in the treatment of melanoma. Nano Research, 2020, 13(8): 2106-2117. https://doi.org/10.1007/s12274-020-2817-6
Topics:
CellsCrystallinityCytologyElectrolytesMammalsNanoparticlesOncologyPathologyTumors

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Received: 25 December 2019
Revised: 13 April 2020
Accepted: 17 April 2020
Published: 05 August 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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