Abstract

Recently there has been a wide concern on inorganic nanoparticles as drug delivery carriers. CaCO3 particles have shown promising potential for the development of carriers for drugs, but little research had been performed regarding their safe dosage for maximizing the therapeutic activity without harming biosystems. In this study, we assessed the biological safety of porous spherical CaCO3 microparticles on Hela cells. The reactive oxygen species (ROS), glutathione (GSH), carbonyl content in proteins (CCP), DNA-protein crosslinks (DPC) and cell viability were measured. Results showed that with the exposure concentration increase, ROS and CCP in Hela cells presented a significant increase but GSH contents in Hela cells and cell viability showed a significant decrease respectively compared with the control. DPC coefficient ascended, but no statistically significant changes were observed. The results indicated that porous spherical CaCO3 microparticles may induce oxidative damage to Hela cells. But compared with other nanomaterials, porous spherical CaCO3 appeared to have good biocompatibility. The results implied that porous spherical calcium carbonate microparticles could be applied as relatively safe drug vehicles, but with the caveat that the effect of high dosages should not be ignored when attempting to maximize therapeutic activity by increasing the concentration.

Highlights

  • During the past decades, inorganic nanoparticles as drug delivery carriers have attracted much attention in modern pharmaceutical and medication area

  • The results indicated that porous spherical CaCO3 microparticles may induce oxidative damage to Hela cells

  • The measurement of CCP showed that the carbonyl content in proteins in Hela cells increased in a concentration-dependent manner (Figure 5), and 400 μg/mL of CaCO3 treatment resulted in a significant increase of carbonyl contents in proteins (p < 0.05) which indicated that CaCO3 microparticles may have harmful effects on these biomacromolecules at the highest concentrations tested

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Summary

Introduction

Inorganic nanoparticles as drug delivery carriers have attracted much attention in modern pharmaceutical and medication area Many inorganic materials, such as calcium phosphate [1], colloidal gold [2], carbon nanotubes [3], silicon [4], iron oxide [5] and layered double hydroxide (LDH) [6] have been studied. These particles could spontaneously load positively charged doxorubicin (DOX) molecules whose releasing from the CaCO3 microparticles could be sustained to more than 150 h. They could exhibit unexpected toxicity to living organisms [13,14,15] It had been mentioned in some reports that CaCO3 microparticles was relatively safe drug carriers, but little research had been performed regarding its safe dosage for maximizing the therapeutic activity without harming biosystems. In the present study, the reactive oxygen species, DNA-protein crosslinks and cell viability were measured to access the biological safety of porous calcium carbonate microparticles on Hela cells

Cell Culture and Exposure to CaCO3 Particles
Intracellular ROS Measurement
Intracellular GSH Measurement
MTT Assay
Results and Discussion
Intracellular GSH Content
CCP Assay
Conclusion
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