Cardiovascular and cerebrovascular diseases induced by atherosclerosis (AS) have become the dominant cause of disability and mortality throughout the world. The typical early pathological process of AS involves the activation of inflammatory macrophages in the vulnerable plaque. In this work, we first employed chitosan-coated carbon nanocages (CS-CNCs) as nanocarriers to load Chlorin e6 (Ce6) and then linked dextran sulfate (DS) to the outermost layer by electrostatic adsorption to create a multifunctional therapeutic nanoplatform, CS-CNCs@Ce6/DS. The DS of the nanoplatform can recognize and bind to the type A scavenger receptor (SR-A), which is expressed only on the activated macrophages of the arterial plaque, so the proposed nanoplatform selectively targets these macrophages and accumulates there. Furthermore, DS can competitively inhibit cellular endocytosis of oxidized low-density lipoproteins via blocking of SR-A. The rapid photothermal conversion capability of CS-CNCs enables efficient therapeutic delivery during photothermal therapy (PTT). Interestingly, near-infrared-accelerated drug release induced by initial 808-nm laser irradiation was observed, thus enhancing the Ce6 concentration in the atherosclerotic plaque area and the efficiency of photodynamic therapy (PDT). Sequential photothermal/ photodynamic ablation of the activated macrophages reduced pro-inflammatory cytokine secretion and alleviated the proliferation and migration of smooth muscle cells. These finally resulted in the stabilization and shrinkage of atherosclerotic plaques, further inhibiting the development and exacerbation of AS. Therefore, this work achieved a "1 + 1 greater than 2" effect by providing a novel approach to the treatment of atherosclerotic plaques, which is promising for the prevention of AS-related diseases.
Highlights A novel model incorporating multiparametric MRI-based radiomic signature with clinically independent risk factors can greatly improve the non-invasive diagnostic accuracy in differentiating PC from MFCP. The nomogram integrating rad-score and clinically independent risk factors had a better diagnostic performance than the mp-MRI and clinical models. The mixed model may aid in formulating treatment strategies and help to avoid unnecessary surgical operations for doctors.
BACKGROUND Stent insertion can effective alleviate the symptoms of benign esophageal strictures (BES). Magnesium alloy stents are a good candidate because of biological safety, but show a poor corrosion resistance and a quick loss of mechanical support in vivo . AIM To test the therapeutic and adverse effects of a silicone-covered magnesium alloy biodegradable esophageal stent. METHODS Fifteen rabbits underwent silicone-covered biodegradable magnesium stent insertion into the benign esophageal stricture under fluoroscopic guidance (stent group). The wall reconstruction and tissue reaction of stenotic esophagus in the stent group were compared with those of six esophageal stricture models (control group). Esophagography was performed at 1, 2, and 3 weeks. Four, six, and five rabbits in the stent group and two rabbits in the control groups were euthanized, respectively, at each time point for histological examination. RESULTS All stent insertions were well tolerated. The esophageal diameters at immediately, 1, 2 and 3 wk were 9.8 ± 0.3 mm, 9.7 ± 0.7 mm, 9.4 ± 0.8 mm, and 9.2 ± 0.5 mm, respectively ( vs 4.9 ± 0.3 mm before stent insertion; P < 0.05). Magnesium stents migrated in eight rabbits [one at 1 wk (1/15), three at 2 wk (3/11), and four at 3 wk (4/5)]. Esophageal wall remodeling (thinner epithelial and smooth muscle layers) was found significantly thinner in the stent group than in the control group ( P < 0.05). Esophageal injury and collagen deposition following stent insertion were similar and did not differ compared to rabbits with esophageal stricture and normal rabbits ( P > 0.05). CONCLUSION Esophageal silicone-covered biodegradable magnesium stent insertion is feasible for BES without causing severe injury or tissue reaction. Our study suggests that insertion of silicone-covered magnesium esophageal stent is a promising approach for treating BES.
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