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.
Precise therapy has become prevalent in clinical practice owing to its accurate and efficient targeting treatment of diseases. Such treatments involving polymersomes as carriers have great potential to lesion sites without damage to normal tissues. However, due to the inherent thick hydrophobic layer of polymersomes, an instantaneous release response to external stimuli remains a challenge. To tackle this challenge, here, we report on the synthesis and applications of azobenzene-containing photochromic vesicles as delivery vectors. These vesicles are assembled from small-molecule amphiphiles that have been developed to provide a fast response and promote instantaneous release due to molecular size reduction compared with macromolecular polymersomes. After cross-linking, the stability of vesicles under a physiological environment is notably enhanced. By varying UV and visible light irradiation, the "gate" of vesicles can be opened and closed reversibly for the controlled release of capsuled cargoes. In vitro experiments display that the vesicles can be applied to load cysteamine for eliminating excess reactive oxygen. The synthesized vesicles here show high performance in controlled and instantaneous release in cells both in time and space. By our approach, oxidative damage to cellular biomolecules can be substantially reduced.
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