Mesoporous Silica Nanoparticles Decorated with Polycationic Dendrimers for Infection Treatment

TL;DR

This study develops mesoporous silica nanoparticles decorated with polycationic dendrimers loaded with antibiotics, demonstrating enhanced bacterial membrane penetration and antimicrobial efficacy against Gram-negative bacteria, offering a promising new infection treatment.

Contribution

It introduces a novel nanoantibiotic system combining mesoporous silica nanoparticles with polycationic dendrimers for improved infection therapy.

Findings

High penetrability of functionalized nanoparticles into Gram-negative bacterial membranes

Effective antibiotic release and antimicrobial activity against bacterial biofilms

Potential for new infection treatment strategies

Abstract

This work aims to provide an effective and novel solution for the treatment of infection by using nanovehicles loaded with antibiotics capable of penetrating the bacterial wall, thus increasing the antimicrobial effectiveness. These nanosystems, named "nanoantibiotics", are composed of mesoporous silica nanoparticles (MSNs), which act as nanocarriers of an antimicrobial agent (levofloxacin, LEVO) localized inside the mesopores. To provide the nanosystem of bacterial membrane interaction capability, a polycationic dendrimer, concretely the poly(propyleneimine) dendrimer of third generation (G3), was covalently grafted to the external surface of the LEVO-loaded MSNs. After physicochemical characterization of this nanoantibiotic, the release kinetics of LEVO and the antimicrobial efficacy of each released dosage were evaluated. Besides, internalization studies of the MSNs functionalized with the G3 dendrimer were carried out, showing a high penetrability throughout Gram-negative bacterial membranes. This work evidences that the synergistic combination of polycationic dendrimers as bacterial membrane permeabilization agents with LEVO-loaded MSNs triggers an efficient antimicrobial effect on Gram-negative bacterial biofilm. These positive results open up very promising expectations for their potential application in new infection therapies.