Biocompatible acid-degradable micro-mesoporous CaCO3:Si:Fe nanoparticles potential for drug delivery

Abstract

Calcium carbonate nanoparticles of 50 nm in diameter are synthesized within the mesoporous silica particles with a subsequent etching out of the template material. Due to interaction of the filler with a template the as-prepared CaCO 3 nanoparticles are doped with Si which allows preserving their small size and porous structure. To make an aggregatively stable aqueous suspension of the nanoparticles they are additionally doped with Fe. The obtained CaCO 3 :Si:Fe nanoparticles possess a micro-mesoporous structure with specific surface area of 205 m 2 g −1 and pore volume of 0.59 cm 3 g −1 . It is shown that the particles are fully dissolved in dilute HCl in several minutes. It is demonstrated that nanoparticles are nontoxic and are able to penetrate across the cell membrane and accumulate in HeLa and K-562 cells. Owing to high adsorption capacity a loading of 25 wt% doxorubicin (DOX) into CaCO 3 :Si:Fe nanopaticles is performed. Being internalized by cells DOX-loaded CaCO 3 :Si:Fe nanoparticles provide greater amount (up to three times) of DOX within the intracellular space compared to free doxorubicin. Encapsulation of the drug into the nanoparticles reduces its toxicity, IC 50 value increases by 2.5 and 5 times for HeLa and K-562 cells, respectively. - Micro-mesoporous CaCO 3 nanoparticles with high porosity were synthesized by hard template method - The CaCO 3 nanoparticles are aggregatively stable in water, not subjected to recrystallization and can be easily dissolved in acidic media - Porous CaCO 3 nanoparticles are non-toxic and easily penetrate across the cell membrane - Encapsulation of Doxorubicin (DOX) into the CaCO 3 nanoparticles substantially reduces toxicity of the drug and provide greater amount of DOX within the intracellular space