Most of the current nanomedicine-based treatments for critical limb ischemia(CLI)only aim at promoting angiogenesis,ignoring the negative influence on the therapeutic effects caused by the complex pathological micro-e...Most of the current nanomedicine-based treatments for critical limb ischemia(CLI)only aim at promoting angiogenesis,ignoring the negative influence on the therapeutic effects caused by the complex pathological micro-environment of ischemic tissue.Herein,near-infrared(NIR)light-driven metal ion(Cu^(2+))-loaded polydopamine(PDA)nanomotors(JMPN@Cu^(2+))is designed and prepared.Due to the good antioxidant and anti-inflammatory activities of PDA,JMPN@Cu^(2+)exhibits excellent biocompatibility and significantly improves the ischemic micro-environment.Additionally,based on superior photothermal conversion effect and jellyfish-like structure,the nanomotors are quickly propelled under NIR laser with low energy intensity to acquire the ability of movement and facilitate intracellular uptake of JMPN@Cu^(2+)by endothelial cells,resulting in the enhanced pro-angiogenic effect of Cu^(2+).Moreover,in vivo experimental findings show that JMPN@Cu^(2+)combined with NIR irradiation can successfully accelerate blood flow recovery and improve muscle repair.Taking these results together,this kind of nanomotor can promote angiogenesis along with ischemic micro-environment amelioration,holding great potential applications for the treatment of limb ischemia.展开更多
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 c...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.展开更多
基金supported by the National Natural Science Foundation of China(No.82170515)Open Research Fund of Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy(No.XZSYSKF2021038)Jiangsu Funding Program for Excellent Postdoctoral Talent,and Changzhou Municipal Health Commission Science and Technology Project(No.ZD202126).
文摘Most of the current nanomedicine-based treatments for critical limb ischemia(CLI)only aim at promoting angiogenesis,ignoring the negative influence on the therapeutic effects caused by the complex pathological micro-environment of ischemic tissue.Herein,near-infrared(NIR)light-driven metal ion(Cu^(2+))-loaded polydopamine(PDA)nanomotors(JMPN@Cu^(2+))is designed and prepared.Due to the good antioxidant and anti-inflammatory activities of PDA,JMPN@Cu^(2+)exhibits excellent biocompatibility and significantly improves the ischemic micro-environment.Additionally,based on superior photothermal conversion effect and jellyfish-like structure,the nanomotors are quickly propelled under NIR laser with low energy intensity to acquire the ability of movement and facilitate intracellular uptake of JMPN@Cu^(2+)by endothelial cells,resulting in the enhanced pro-angiogenic effect of Cu^(2+).Moreover,in vivo experimental findings show that JMPN@Cu^(2+)combined with NIR irradiation can successfully accelerate blood flow recovery and improve muscle repair.Taking these results together,this kind of nanomotor can promote angiogenesis along with ischemic micro-environment amelioration,holding great potential applications for the treatment of limb ischemia.
基金the National Natural Science Foundation of China(Nos.81870351,31771097,81972899)National Key Research and Development Project of China(No.2018YFC2000301)+4 种基金CAMS Innovation Fund for Medical Sciences(CIFMS.2018-I2M-1-002,2017-I2M-1-016)PUMC Discipline Construction Project(No.201920102101)Natural Science Foundation of Beijing Municipality(No.7192186)Fundamental Research Funds for the Central Universities(Nos.3332018185,3332018174)Beijing Hospital Project(No.BJ2018038).
文摘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.
