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

Li, Na; Cui, Wei; Cong, Peifang; Tang, Jie; Guan, Yong; Huang, Caihao; Liu, Yunen; Yu, Chengzhong et al. · Bioact Mater · 2021

basic_science · Level V

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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 Ca<sup>2+</sup> 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 <i>in vitro</i> and <i>in vivo</i> results preliminarily demonstrated good biosafety of the inorganic-organic Mg-ACP/PAA hybrid nanoparticles, which may have potential for biomedical applications.