Superparamagnetic Iron Oxide Nanoparticles Decorated Mesoporous Silica Nanosystem for Combined Antibiofilm Therapy.

Elena Álvarez,María Del Puerto Morales,Rafael R Castillo,Alvaro Gallo-Cordova,Montserrat Colilla,María Vallet-Regí,Blanca González,Manuel Estévez,Isabel Izquierdo-Barba

doi:10.3390/pharmaceutics14010163

Abstract

A crucial challenge to face in the treatment of biofilm-associated infection is the ability of bacteria to develop resistance to traditional antimicrobial therapies based on the administration of antibiotics alone. This study aims to apply magnetic hyperthermia together with controlled antibiotic delivery from a unique magnetic-responsive nanocarrier for a combination therapy against biofilm. The design of the nanosystem is based on antibiotic-loaded mesoporous silica nanoparticles (MSNs) externally functionalized with a thermo-responsive polymer capping layer, and decorated in the outermost surface with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are able to generate heat upon application of an alternating magnetic field (AMF), reaching the temperature needed to induce a change in the polymer conformation from linear to globular, therefore triggering pore uncapping and the antibiotic cargo release. The microbiological assays indicated that exposure of E. coli biofilms to 200 µg/mL of the nanosystem and the application of an AMF (202 kHz, 30 mT) decreased the number of viable bacteria by 4 log10 units compared with the control. The results of the present study show that combined hyperthermia and antibiotic treatment is a promising approach for the effective management of biofilm-associated infections.

Highlights

Bacterial infections pose a serious threat to public health, becoming the second leading cause of death worldwide [1,2,3], with biofilms being the main cause of most resistant infections [1,4]
We have investigated the antibacterial efficacy of magnetic a new multicomponent the alternating magnetic field (AMF)-triggered delivery of a broad-spectrum antibiotic with hyperthermia nanosystem, noticing the enhanced effect produced by the combination of hyperthermia for the local treatment of biofilm-associated bacterial infections as a proof of concept
The results obtained show relevant data in terms of. This multicomponent nanosystem consists of mesoporous silica nanoparticles (MSNs), bactericidal being reflected in a viability reductioncoated of almost four units in the log10 loaded withefficacy, the broad-spectrum antibiotic levofloxacin, with a thermosensitive with respect to the control

Summary

Introduction

Bacterial infections pose a serious threat to public health, becoming the second leading cause of death worldwide [1,2,3], with biofilms being the main cause of most resistant infections [1,4]. Biofilms are communities of microorganisms that are covered by a protective extracellular matrix This self-produced matrix protects the bacteria from hostile environmental conditions, reduces the efficacy of antibiotics compared with the effect in their planktonic counterparts and is responsible for the increased resistance to antimicrobials [4,5]. It has been shown that bacteria in biofilms can tolerate antibiotics at concentrations up to 1000 times higher than bacteria in a planktonic state [6,7] Both the prevalence of antibiotic resistance and the increase in biofilm-associated infections are driving the demand for new, advanced and more effective treatments for such infections [8,9,10]. Mesoporous silica nanoparticles (MSNs) present attractive characteristics, such as their thermal/mechanical stability, adjustable pore

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