Isaac Scientific Publishing

Journal of Advances in Nanomaterials

Study on the Biological Safety of Arginine-modified Hydroxyapatite Nanoparticles

Download PDF (1227 KB) PP. 95 - 104 Pub. Date: December 20, 2016

DOI: 10.22606/jan.2016.12006


  • Min Yang1, Junjie Sun1, Yanzhong Zhao1, 2,**
    1The Third Xiangya Hospital, Central South University, Changsha 410013, China
  • Zewen Song1, Haibin Zhang1, Shaihong Zhu1, 2

    2Research Center for Medical Material and Instruments, Central South University, Changsha 410013, China


This study was to investigate the biological safety of arginine-modified hydroxyapatite nanoparticles (HAP/Arg) as a gene carrier for gene therapy. Experiments were conducted on normal human vascular endothelial cells (HAEC) and human tumor cells (Hela cells) to study the biological safety of HAP/Arg at subcellular level, cellular level, and overall level of animal. Cell proliferation, structural integrity of cell membrane, acute toxicity of HAP/Arg and animal reproductive toxicity of HAP/Arg were all examined. The results showed that HAP/Arg of various doses did not significantly affect normal growth and cell membrane structure of HAEC cells and Hela cells, when these cells were treated for different duration. Acute toxicity experiments and general reproductive toxicity experiments on animals also revealed no significant difference between each HAP/Arg dose group and control group. These results could lay the foundation for the construction of a novel and safe HAP gene delivery system.


Hydroxyapatite, gene carrier, arginine-modification, biological safety.


[1] S.H. Zhu, B.Y. Huang, K.C. Zhou, S.P. Huang, F. Liu, and Y.M. Li, “Hydroxyapatite Nanoparticles as a Novel Gene Carrier,”Journal of Nanoparticle Research, vol. 22,no. 5, pp.980–984,2005.

[2] T.N. Do, W.H. Lee, C.Y. Loo, A.V. Zavgorodniy, and R. Rohanizadeh, “Hydroxyapatite nanoparticles as vectors for gene delivery,”Therapeutic Delivery, vol. 3,no. 5, pp.623–632,2012.

[3] G. Zuo, Y. Wan, and Y. Zhang, “Preparation and characterization of a novel laminated magnetic hydroxyapatite for application on gene delivery,”Materials Letters, vol. 68, pp.225–227,2012.

[4] H. Sun, M. Jiang, and S.H. Zhu, “In vitro and in vivo studies on hydroxyapatite nanoparticles as a novel vector for inner ear gene therapy,”Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, vol. 43,no. 1, pp.51–57,2008.

[5] Y.Z. Zhao, S.H. Zhu, J. Tan, Y.Y. Huang, Zh.Y. Li, and K.C. Zhou,“Arginine modification and gene binding of hydroxyapatite nanoparticles,”Zhongguo Youse Jinshu Xuebao/chinese Journal of Nonferrous Metals,vol.20,no.6, pp.1203–1208,2010.

[6] G.H. Wang, Y.Z. Zhao, J.Tan, S.H. Zhu, and K.C. Zhou,“Arginine functionalized hydroxyapatite nanoparticles and its bioactivity for gene delivery,”Transactions of Nonferrous Metals Society of China,vol.25,no.2, pp.490–496,2015.

[7] Z. Siprashvil, F.A. Scholl, S.F. Oliver, A. Adams, C.H. Contag, P.A. Wender, and P.A. Khavari,“Gene transfer via reversible plasmid condensation with cysteine-flanked, internally spaced arginine-rich peptides,”Human Gene Therapy, vol.14, no.13, pp.1225–1233,2003.

[8] S. Futaki, W. Ohashi, T. Suzuki, M. Niwa, S. Tanaka, K. Ueda, H. Harashima, and Y. Sugiura, “Stearylated ariginine-rich peptides: A new class of transfection systems,”Bioconjugate Chemistry,vol.12, no.6, pp.1005–1011,2001.

[9] A.D.Maynard, “Nanotechnology:assessing the risk,”Nano Today, vol.1, no.2, pp.22-33,2006.

[10] W. Hannah, and P.B. Thompson,“Nanotechnology,risk and the environment:a review,”Journal of Environmental Monitoring Jem,vol.10, no.3, pp.291-300, 2008.

[11] A. Maynard, and D. Rejeski,“Too small to overlook,”Nature, vol.460, no.7252, pp.174-174, 2009.

[12] A.M. Fan, and G. Alexeeff, “Nanotechnology and nanomaterials: toxicology, risk assessment, and regulations,”Journal of Nanoscience and Nanotechnology, vol.10, no.12, pp.8646-8657, 2010.

[13] E.M. Forsberg,“Standardisation in the field of nanotechnology: some issues of legitimacy,”Science and Engineering Ethics,vol.18, no.4, pp.719-739,2012.

[14] A. Besinis,T. De-Peralta,C.J.Tredwin, and R.D.Handy, “Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits,”ACS Nano, vol.9, no.3, pp.2255–2289,2015.

[15] R.Z. Legeros,“Properties of osteoconductive biomaterials: calciumphosphates,”Clinical Orthopaedics and Related Research,vol.395, no.395, pp.81-98,2002.

[16] H.Aoki, and T.Kutsuno, “An in vivo study on the reaction of hydroxyapatite-sol injected into blood,” Journal of Materials Science:Materials in Medicine,vol.11, no.2, pp.67-72,2000.

[17] J.L. Tang, and T.F. Xi,“Research status of the biological safety of nano-hydroxyapatite,” Journal of Clinical Rehabilitative Tissue Engineering Research,vol.11, no.5, pp.936-943,2007.

[18] G. Oberdorster, Z. Sharp, V. Atudorei, A. Elder, R. Gelein, A. Lunts, W. Kreyling, and C. Cox, “Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats,”Journal of Toxicology and Environmental Health Part A,vol.65, no.20, pp.1531-1543,2002.

[19] X. Wu, Y. Tan,H. Mao, and M. Zhang,“Toxic effects of iron oxide nanoparticles on human umbilical vein endothelial cells,”International Journal of Nanomedicine,vol.5,no.1,pp.385-399,2010.

[20] Y.Sh. Dong,“The establishment and practice of a standard toxicopathological platform in drug safety evaluation,”Beijing: The Chinese people's Liberation Army Military Medical Science Academy,2012.

[21] D.R. Joseph, L. Demin, and W.B. Lin, “Nanoscale metal-organic frameworks for biomedical imaging and drug delivery,”Acc.chem.res,vol.44,no.10,pp.957-968,2011.

[22] J.N. Liu, X.L. Wei, H. Jiang, and W.Zh. Zhong,“Preparation and Transfer Efficiency of Modified PAMAM Dendrimer Gene Delivery,”Journal of Huazhong Agricultural University,vol.29,no.3,pp.333-334,2010.