Dissolving Hydroxyolite: A DNA Molecule into Its Hydroxyapatite Mold

Abstract

Abstract:In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that controls its dissolution in acidic environments remains unclear. Knowledge of such process is highly desirable to provide better understanding of different pathologies, as for example osteoporosis, and of the HAp potential as vehicle for gene delivery to replace damaged DNA. In this work, the mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has been investigated at the atomistic level using computer simulations. For this purpose, four consecutive (multi-step) molecular dynamics simulations, involving different temperatures and proton transfer processes, have been carried out. Results are consistent with a polynuclear decalcification mechanism in which proton transfer processes, from the surface to the internal regions of the particle, play a crucial role. Besides, the DNA remains protected by the mineral mold and transferred proton from both temperature and chemicals. These results, which indicate that biomineralization imparts very effective protection to DNA, also have important implications in other biomedical fields, as for example in the design of artificial bones or in the fight against osteoporosis by promoting the fixation of Ca 2+ ions.

Biodegradable Inorganic Nanostructured Biomaterials for Drug Delivery

“…[ 12c,14 ] 2)Synthetic calcium phosphate nanocarriers can degrade into nontoxic Ca 2+ and PO 4 3− ions in a weak acidic environment in vivo, and these ions can participate in the normal metabolism of the human body and have no long‐term toxicity problem. [ 15 ] 3)The surface of calcium phosphate nanocarriers has abundant –OH groups, Ca 2+ , and PO 4 3− ions, which can effectively adsorb drug molecules by electrostatic interaction. [ 16 ] For example, the surface of calcium phosphate nanocarriers can effectively adsorb drug molecules with acid groups such as carboxylic (–COOH) and phosphoric groups.…”

“…[ 17 ] 4)The solubility of calcium phosphate nanocarriers increases with decreasing pH value, leading to pH‐responsive drug delivery performance. [ 15,18 ] Based on this property, calcium phosphate materials were used as an ideal gatekeeper for pH‐responsive drug release. [ 19 ] In addition, different crystalline phases of calcium phosphate nanocarriers exhibit different dissolution rates.…”

“…Bertran et al. [ 15 ] studied the dissolution mechanism of HAP nanoparticles encapsulating double‐stranded DNA molecules in the acidic environment at the atomic level using computer simulations. They demonstrated a polynuclear decalcification mechanism in which the proton transfer process from the surface to internal regions of the particle played a crucial role.…”

Biodegradable and Biocompatible Systems Based on Hydroxyapatite Nanoparticles

“…Mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has recently been investigated at the atomistic level using computer simulations [130]. Results indicated a polynuclear decalcification mechanism with significant transfer processes, from the surface to the internal regions of the particle.…”

Morphology, Structure Evolution and Site‐Selective Occupancy of Eu3+ in Ca10(PO4)6(OH)2 Nanorods Synthesized via Subcritical Hydrothermal Method

“…Crystal size and shape of hydroxyapatite affects the biological demineralization process, which is important for understanding the Ca‐loss in bone and teeth that induces osteoporosis. However, the mechanism for Ca 2+ loss in hydroxyapatite‐based tissue and organ remains unclear . The control of site‐occupancy of doped rare‐earth cations in the definite crystallographic site of hydroxyapatite may provide a model material to monitor the Ca‐loss, which is important for further understanding the osteoporosis or progressive bone loss.…”