Biomimetic inorganic-organic hybrid nanoparticles from magnesium-substituted amorphous calcium phosphate clusters and polyacrylic acid molecules

Na Li; Wei Cui; Peifang Cong; Jie Tang; Yong Guan; Caihao Huang; Yunen Liu; Chengzhong Yu; Rui Yang; Xing Zhang

doi:10.1016/j.bioactmat.2021.01.005

Biomimetic inorganic-organic hybrid nanoparticles from magnesium-substituted amorphous calcium phosphate clusters and polyacrylic acid molecules

Bioact Mater. 2021 Jan 23;6(8):2303-2314. doi: 10.1016/j.bioactmat.2021.01.005. eCollection 2021 Aug.

Authors

Na Li^{1

2}, Wei Cui^{1

2}, Peifang Cong³, Jie Tang⁴, Yong Guan⁵, Caihao Huang^{1

2}, Yunen Liu³, Chengzhong Yu⁴, Rui Yang^{1

2}, Xing Zhang^{1

2}

Affiliations

¹ Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China.
² School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.
³ Department of Emergency Medicine, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110016, China.
⁴ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁵ National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui, 230029, China.

Abstract

Amorphous calcium phosphate (ACP) has been widely found during bone and tooth biomineralization, but the meta-stability and labile nature limit further biomedical applications. The present study found that the chelation of polyacrylic acid (PAA) molecules with Ca²⁺ ions in Mg-ACP clusters (~2.1 ± 0.5 nm) using a biomineralization strategy produced inorganic-organic Mg-ACP/PAA hybrid nanoparticles with better thermal stability. Mg-ACP/PAA hybrid nanoparticles (~24.0 ± 4.8 nm) were pH-responsive and could be efficiently digested under weak acidic conditions (pH 5.0-5.5). The internalization of assembled Mg-ACP/PAA nanoparticles by MC3T3-E1 cells occurred through endocytosis, indicated by laser scanning confocal microscopy and cryo-soft X-ray tomography. Our results showed that cellular lipid membranes remained intact without pore formation after Mg-ACP/PAA particle penetration. The assembled Mg-ACP/PAA particles could be digested in cell lysosomes within 24 h under weak acidic conditions, thereby indicating the potential to efficiently deliver encapsulated functional molecules. Both the in vitro and in vivo results preliminarily demonstrated good biosafety of the inorganic-organic Mg-ACP/PAA hybrid nanoparticles, which may have potential for biomedical applications.

Keywords: ACP clusters; Cellular degradation; Cryo-soft X-ray tomography; Inorganic-organic hybrid; pH responsive.