The human health is still threatened by refractory keratitis and diabetic foot ulcers caused by bacterial infections, hypoxia, and chronic inflammation, so that patients are exposed to the risk of amputation, vision loss, and even death. Herein, an oxygen-producing double-layered hydrogel is developed that can visualize bacterial infections and supply oxygen to enhance antimicrobial photodynamic therapy (PDT) and inflammation alleviation for diabetic wounds healing. The inner layer hydrogel (containing oxidized sodium alginate/carboxymethyl chitosan [CMCS] via Schiff-base) is incorporated with a photodynamic metal-organic framework (PCN-224) and a pH indicator (bromothymol blue). The outer layer hydrogel (containing agarose and CMCS) loads photosynthetic cyanobacteria that continuously generate oxygen to relieve hypoxia of tissue and enhance antimicrobial PDT efficiency. Meanwhile, some unique advantages are reflected by continuous oxygen supply under natural light, such as cell migration acceleration, inflammation relief, promotion of skin capillary formation, and wound tissue recovery. Therefore, the self-oxygenated double-layered hydrogel offers tremendous benefits in the synergistic treatment of refractory anaerobe wounds from timely infection monitoring to tissue repair.
Low-temperature
photothermal therapy (PTT) systems constructed
by integrating organic photothermal agents with other bactericidal
components that initiate bacterial apoptosis at low hyperthermia possess
a promising prospect. However, these multicomponent low-temperature
PTT nanoplatforms have drawbacks in terms of the tedious construction
process, suboptimal synergy effect of diverse antibacterial therapies,
and high laser dose needed, compromising their biosafety in ocular
bacterial infection treatment. Herein, a mild PTT nanotherapeutic
platform is formulated via the self-assembly of a
pH-responsive phenothiazinium dye. These organic nanoparticles with
photothermal conversion efficiency up to 84.5% necessitate only an
ultralow light dose of 36 J/cm2 to achieve efficient low-temperature
photothermal bacterial inhibition at pH 5.5 under 650 nm laser irradiation.
In addition, this intelligent mild photothermal nanoplatform undergoes
negative to positive charge reversion in acid biofilms, exhibiting
good penetration and highly efficient elimination of drug-resistant E. coli biofilms under photoirradiation. Further in vivo animal tests demonstrated efficient bacterial elimination
and inflammatory mitigation as well as superior biocompatibility and
biosafety of the photothermal nanoparticles in ocular bacterial infection
treatment. Overall, this efficient single-component mild PTT system
featuring simple construction processes holds great potential for
wide application and clinical transformation.
According to International Diabetes Federation Diabetes Atlas statistics, diabetic retinopathy (DR) is the leading cause of vision loss in blinding diseases. The underlying cause of retinal vasculopathy progression in diabetic patients is hyperglycemia and hypoxia features in microvascular region. Hence, cyanobacteria are used as carriers to load both gold nanoparticles (Au NPs) with glucose oxidase‐like activity and iridium nanoparticles (Ir NPs) with catalase‐like activity, respectively (Cyano@Au@Ir). The Au NPs nanozyme first degrades glucose into hydrogen peroxide, which is further decomposed into H2O and O2 by the Ir NPs to complete the cascade hypoglycemic reaction. Based on the unique light transmittance of eyeball and the accumulation of light in the retinal area, the sustainable O2 production by Cyano greatly alleviates the hypoxia of microenvironment, leading to the decrease of angiogenic growth factor and hypoxia‐inducible factor expressions. Simultaneously, the highly expressed peroxide in the DR microenvironment can also be eliminated by Ir NPs for anti‐inflammatory property. Furthermore, it is demonstrated in DR animal model that Cyano@Au@Ir significantly reduces neovascular progression and vascular leakage. This novel treatment mode fundamentally degrades blood glucose, continuously supplies O2, and scavenges free radicals for comprehensive microenvironment regulation, providing inspirations for solving fundus complications of DR.
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