pH-Triggered Controllable Release of Silver-Indole-3 Acetic Acid Complexes from Mesoporous Silica Nanoparticles (IBN-4) for Effectively Killing Malignant Bacteria

摘要

An efficient approach for the antimicrobial agent delivery specifically at acidic pH has been proposed. At the outset, functionalized mesoporous nanoparticles (NPs) were examined to verify the success of synthesis while considering the structural properties by various characterizations. The NPs were immobilized with silver indole-3 acetic acid hydrazide (IAAH-Ag) complexes via a pH-sensitive hydrazone bond, which functioned as a model drug. When the transitional metal complexes with IBN-4-IAAH-Ag were exposed to acidic pH (near pH 5.0), the silver ions were preferentially released (70%) in a controlled manner up to 12 h by pH-sensitive denial of hydrazone bonds. In contrary, a low drug release (about 25%) was seen in physiological buffer (pH 7.4) demonstrating the pH sensitive release of this drug. Furthermore, the antibacterial efficacy of this unique structured sample was tested against the planktonic cells and biofilms of Gram-positive and Gram-negative bacteria with field emission scanning electron microscope in turn measuring the growth curves, formation of lethal reactive oxygen species, protein leakage, and DNA damage. The synthesized pH-sensitive IAAH-Ag complex was found to have high antimicrobial efficacy against multidrug resistant clinical isolates both in planktonic and biofilm states. Going forward, the synthesized nanoconjugates proved a good in vivo efficacy in treating the bacterial infection of mice. These new metal complex-conjugated NPs through a pH-sensitive hydrazone bond opened up a new avenue for the design and synthesis of the next generation antibacterial agents, which would act as an alternative to antibiotics.