Amine-Functionalized Mesoporous Silica Nanoparticles: A New Nanoantibiotic for Bone Infection Treatment

Abstract

This manuscript reports an effective new alternative for the management of bone infection by the development of an antibiotic nanocarrier able to penetrate bacterial biofilm, thus enhancing antimicrobial effectiveness. This nanosystem, also denoted as "nanoantibiotic", consists in mesoporous silica nanoparticles (MSNs) loaded with an antimicrobial agent (levofloxacin, LEVO) and externally functionalized with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (DAMO) as targeting agent. This amine functionalization provides MSNs of positive charges, which improves the affinity towards the negatively charged bacteria wall and biofilm. Physical and chemical properties of the nanoantibiotic were studied using different characterization techniques, including Xray diffraction (XRD), transmission electron microscopy (TEM), N 2 adsorption porosimetry, elemental chemical analysis, dynamic light scattering (DLS), zeta (ζ )-potential and solid-state nuclear magnetic resonance (NMR). "In vial" LEVO release profiles and the in vitro antimicrobial effectiveness of the different released doses were investigated. The efficacy of the nanoantibiotic against a S. aureus biofilm was also determined, showing the practically total destruction of the biofilm due to the high penetration ability of the developed nanosystem. These findings open up promising expectations in the field of bone infection treatment.

Silica Nanoparticles—A Versatile Tool for the Treatment of Bacterial Infections

“…Charge of a nanocarrier can invariably affect its ability to interact with negatively charged bacterial membrane and influence its selectivity. Pedraza and team designed a “nanoantibiotic” system made of MSN loaded with levofloxacin (LEVO) and surface functionalized with positively-charged N -(2-aminoethyl)-3-aminopropyltrimethoxysilane (DAMO) which acts as a targeting agent rendering affinity toward negatively-charged bacterial membrane and biofilms (Pedraza et al, 2018 ). Antibiofilm activity of the this LEVO-loaded nanocarrier against S. aureus indicated a complete destruction biofilm post-treatment.…”

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…In this manner, it is easier for the particles to diffuse into the biofilm to then interact with bacteria and exert their therapeutic effect. Examples of this approach include the use of short positively charged alkoxysilanes [187] or third-generation dendrimers, with a great number of positive charges that allow permeating the bacteria wall and inducing MSN internalization [188]. Besides using positively charged MSNs, lectins have been shown to be effective in targeting and promoting internalization of MSNs into the biofilm, as a consequence of the presence of glycan-type polysaccharides in this protective matrix.…”

Targeted Stimuli-Responsive Mesoporous Silica Nanoparticles for Bacterial Infection Treatment

“…In this line, the group of Prof. Vallet-Regí reported the design of “nanoantibiotics” consisting of antibiotic-loaded MSNs functionalized with positively charged moieties as the targeting agents [ 47 , 68 ]. Thus, MSNs were externally modified with N-(2-aminoethyl)-3-aminopropyltrimethoxy-silane (DAMO) and loaded with the antibiotic LVX [ 68 ]. Amine functionalization provided MSNs of positive charges that improved the ability of the nanosystem to target and penetrate S. aureus biofilm.…”