Highly sensitive H_(2)O_(2)-scavenging nano-bionic system for precise treatment of atherosclerosis

In atherosclerosis,chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species(ROS).In this study,we devised a highly sensitive H_(2)O_(2)-scavenging nanobionic system loaded with probucol(RPP-PU),to treat atherosclerosis more effectively.The RPP material had high sensitivity to H_(2)O_(2),and the response sensitivity could be reduced from 40 to 10μmol/L which was close to the lowest concentration of H_(2)O_(2)levels of the pathological environment.RPP-PU delayed the release and prolonged the duration of PU in vivo.In Apolipoprotein E deficient(ApoE-/-)mice,RPP-PU effectively eliminated pathological ROS,reduced the level of lipids and related metabolic enzymes,and significantly decreased the area of vascular plaques and fibers.Our study demonstrated that the H_(2)O_(2)-scavenging nanobionic system could scavenge the abundant ROS in the atherosclerosis lesion,thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

Significant difference between sirolimus and paclitaxel nanoparticles in antiproliferation effect in normoxia and hypoxia: The basis of better selection of atherosclerosis treatment

Compared with paclitaxel,sirolimus has been more used in the treatment of vascular restenosis gradually as an anti-proliferative drug,but few basic studies have elucidated its mechanism.The anti-proliferative effects of sirolimus or paclitaxel have been demonstrated by numerous studies under normoxia,but few studies have been achieved focusing hypoxia.In this study,porcine carotid artery injury model and classical cobalt chloride hypoxia cell model were established.Sirolimus nanoparticles(SRM-NPs),paclitaxel nanoparticles(PTX-NPs)and blank nanoparticles(Blank-NPs)were prepared respectively.The effect of RPM-NPs on the degree of stenosis,proliferative index and the expression of PCNA after 28 days of porcine carotid artery injury model was evaluated.Compared with saline group and SRM groups,SRM-NPs group suppressed vascular stenosis,proliferative index and the expression of PCNA(P<0.01 and P<0.05).Endothelial cell(EC)and smooth muscle cell(SMC)were pre-treated with cobaltous chloride,followed by SRM-NPs,PTX-NPs,Blank-NPs or PBS control treating,the effects on cell proliferation,HIF-1 expression and glycolysis were detected.SRM-NPs could inhibit EC and SMC proliferation under hypoxia,while PTX-NPs couldn't(P<0.001).Significant differences between sirolimus and paclitaxel NPs in anti-proliferation effect under normoxia and hypoxia may due to the different inhibitory effects on HIF-1αexpression and glycolysis.In conclusion,these results suggest that sirolimus can inhibit the proliferation of hypoxic cells more effectively than paclitaxel.These observations may provide a basis for understanding clinical vascular stenosis therapeutic differences between rapamycin and paclitaxel.

ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia

The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement.Zinc ions have been reported to stimulate angiogenesis,but application was limited to the toxicity concerns.We hypothesized that zinc based metal-EGCG capsule(EGCG/Zn Ps)can achieve sustained release Zn2+resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG.The surface morphology,zeta potential,infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured.In vitro,EGCG/Zn showed significantly antioxidant,antiinflammatory and induced cell migration effect.In addition,EGCG/Zn Ps enabled the sustained release of zinc ions,which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor(VEGF)in vitro and in vivo.In mouse models of limb ischemia,EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues.Moreover,EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score,limb temperature and blood flow than other groups.In conclusion,EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+and EGCG,thus enabling the direct application to limb ischemia.