Surface-Charge-Switchable and Size-Transformable Thermosensitive Nanocomposites for Chemo-Photothermal Eradication of Bacterial Biofilms in Vitro and in Vivo

Abstract

The appearance of multidrug-resistant bacteria and their biofilms presents a serious threat to modern medical systems. Herein, we fabricated a novel gold-nanorod-based chemo-photothermal-integrated antimicrobial platform with surface-charge-switchable and near-infrared (NIR)-induced size-transformable activities that show an enhanced killing efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in both planktonic and biofilm phenotypes. The nanocomposites are prepared by in situ copolymerization using N-isopropyl acrylamide (NIPAM), acrylic acid (AA), and N-allylmethylamine (MAA) as monomers on the surfaces of gold nanorods (GNRs). Ciprofloxacin (CIP) is loaded onto polymer shells of nanocomposites with a loading content of 9.8%. The negatively charged nanocomposites switch to positive upon passive accumulation at the infectious sites, which promotes deep biofilm penetration and bacterial adhesion of the nanoparticles. Subsequently, NIR irradiation triggers the nanocomposites to rapidly shrink in volume, further increasing the depth of biofilm penetration. The NIR-triggered, ultrafast volume shrinkage causes an instant release of CIP on the bacterial surface, realizing the synergistic benefits of chemo-photothermal therapy. Both in vitro and in vivo evidence demonstrate that drug-loaded nanocomposites could eradicate clinical MRSA biofilms. Taken together, the multifunctional chemo-photothermal-integrated antimicrobial platform, as designed, is a promising antimicrobial agent against MRSA infections.

Nanotechnologies for control of pathogenic microbial biofilms

“…108 Photodynamic therapy (PDT) and photothermal therapy (PTT) have also been suggested as possible methods of biofilm targeting. [115][116][117] They are considered to be minimally invasive and reliable. In these methods, reactive oxygen species (ROS) This journal is © The Royal Society of Chemistry 2022 that affect bacterial cells and the biofilm at large through oxidation are generated as a result of irradiation and release of photosensitizers and other loaded agents, respectively, by light of fixed wavelength.…”

Metal and Metal Oxide Nanomaterials for Fighting Planktonic Bacteria and Biofilms: A Review Emphasizing on Mechanistic Aspects

“…The era of antibiotics is progressively coming to an end due to the emergency of multidrug-resistant bacteria. It has been reported that multidrug-resistant bacteria cause at least 700,000 deaths worldwide each year, including 23,000 deaths in the United States and 25,000 deaths in the European Union [ 3 ]. The World Health Organization predicts that 10 million people worldwide will die from bacterial infections by 2050 if no efforts are made to reduce bacterial resistance or develop new antibiotics [ 4 ].…”

Breaching Bacterial Biofilm Barriers: Efficient Combinatorial Theranostics for Multidrug-Resistant Bacterial Biofilms with a Novel Penetration-Enhanced AIEgen Probe

“…Antibacterial agents involve antibiotics, natural extracts, cationic polymers, antimicrobial peptides, , and antibacterial materials. − Most of them are not able to pass through the biofilm barriers efficiently, thus limiting their efficacies in the therapy of biofilm-associated infection. Mature biofilms act as barriers to antimicrobial agents by restricting their diffusion and preventing them from penetrating deeply into the matrix. − Thus, novel therapeutic agents and strategies capable of fully accessing inside bacteria by penetrating the biofilm barriers for tackling biofilms are urgently needed .…”