Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can ...Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate(Cu-EGCG)nano-capsules.The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).It could also promote the proliferation and migration of L929 fibroblasts.In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect.Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group.The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.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
Ulcerative colitis(UC)is characterized by chronic inflammatory processes of the intestinal tract of unknown origin.Current treatments lack understanding on how to effectively alleviate oxidative stress,relieve inflamm...Ulcerative colitis(UC)is characterized by chronic inflammatory processes of the intestinal tract of unknown origin.Current treatments lack understanding on how to effectively alleviate oxidative stress,relieve inflammation,as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously.In this study,a novel drug delivery system based on a metal polyphenol network(MPN)was constructed via metal coordination between epigallocatechin gallate(EGCG)and Fe^(3+).Curcumin(Cur),an active polyphenolic compound,with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN.The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical(O_(2)•-)as well as hydroxyl radical(⋅OH).By hitchhiking yeast microcapsule(YM),Cur-MPN was then encapsulated into YM to obtain CM@YM.Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon.When administered orally,CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS,reducing pro-inflammatory cytokines,and regulating the polarization of macrophages to M1,thus restoring barrier function and maintaining intestinal homeostasis.Importantly,CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids(SCFA)(such as acetic acid,propionic acid,and butyric acid).Collectively,with excellent biocompatibility,our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.展开更多
Fenton reaction centered ferroptosis-apoptosis synergetic therapy has emerged as a promising tumor elimination strategy.However,the low intracellular Fenton level and accumulation of therapeutics at the lesion site gr...Fenton reaction centered ferroptosis-apoptosis synergetic therapy has emerged as a promising tumor elimination strategy.However,the low intracellular Fenton level and accumulation of therapeutics at the lesion site greatly limit the efficacy of ferroptosis therapy.To overcome these two bottlenecks,an inhalable metal polyphenol network(MPN)-hybrid liposome,encoded as LDG,was proposed for enhancing the intracellular Fenton reaction level by co-delivering the ferroptosis inducer dihydroartemisinin(DHA)and the ferrous ion(Fe2+)donor MPN.The synthesized LDG had excellent nebulization performance which significantly improved the accumulation in the lungs,about 8.2 times of intravenous injection.In terms of anticancer mechanisms,MPN raised the intracellular level of Fe2+by constructing iron cycling in the weakly acidic environment of tumors.Triggered by Fe2+,DHA with peroxide-bridge structure underwent a high level of Fenton-like reaction,promoted the production of intracellular reactive oxygen species(ROS)and induced strong ferroptosis while cooperating with apoptosis.LDG exhibited extraordinary antitumor ability in an orthotopic lung tumor model,whose tumor inhibition efficiency was 1.53(P=0.0014)and 1.32(P=0.0183)times of the LG group(liposomes coated with gallic acid(GA)-Fe MPN)and LD group(liposomes loaded with DHA),respectively,showing the strongest anticancer effect.In conclusion,the constructed MPN-hybrid liposomes could be a potent custom nanoplatform for pulmonary delivery and underscored the great potential of ferroptosis-apoptosis synergetic therapy.展开更多
基金funded by National Key Research and Development Program of China(2017YFA0105602,2018YFA0108700)NSFC Projects of INTERNATIONAL COOPERATION and Exchanges(81720108004)+6 种基金National Natural Science Foundation of China(81974019,82100275)Guangdong Provincial Special Support Program for Prominent Talents(2021JC06Y656)Science and Technology Planning Project of Guangdong Province(2020B1111170011,2022B1212010010)Guangdong special funds for science and technology innovation strategy,China(Stability support for scientific research institutions affiliated to Guangdong Province-GDCI 2021)Guangzhou Science and Technology Plan Project(202201000006)The Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(DFJH201812,KJ012019119,KJ012019423)The Marine Economy Development Project of Department of Natural Resources of Guangdong Province(No.GDNRC[2022]039).
文摘Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate(Cu-EGCG)nano-capsules.The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).It could also promote the proliferation and migration of L929 fibroblasts.In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect.Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group.The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.
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.
基金supported by the National Natural Science Foundation of China(Nos.52103183,32360176)the Shaanxi Province Key Research and Development Program(No.2023-YBSF-072)+3 种基金the Natural Science Basic Research Program of Shaanxi(Nos.2021JQ-382,2024JC-YBMS-664)the Fundamental Research Funds for the Central Universities,China(No.xtr052023008)the Innovation Team of Xi’an Medical University(No.2021TD15)the Young Talent Support Plan of Xi’an Jiaotong University,China(No.YX6J001).
文摘Ulcerative colitis(UC)is characterized by chronic inflammatory processes of the intestinal tract of unknown origin.Current treatments lack understanding on how to effectively alleviate oxidative stress,relieve inflammation,as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously.In this study,a novel drug delivery system based on a metal polyphenol network(MPN)was constructed via metal coordination between epigallocatechin gallate(EGCG)and Fe^(3+).Curcumin(Cur),an active polyphenolic compound,with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN.The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical(O_(2)•-)as well as hydroxyl radical(⋅OH).By hitchhiking yeast microcapsule(YM),Cur-MPN was then encapsulated into YM to obtain CM@YM.Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon.When administered orally,CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS,reducing pro-inflammatory cytokines,and regulating the polarization of macrophages to M1,thus restoring barrier function and maintaining intestinal homeostasis.Importantly,CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids(SCFA)(such as acetic acid,propionic acid,and butyric acid).Collectively,with excellent biocompatibility,our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.
基金the National Natural Science Foundation of China(Nos.82104070 and 82373800)Guangdong Universities Keynote Regions Special Funded Project(No.2022ZDZX2002)General Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20241071).
文摘Fenton reaction centered ferroptosis-apoptosis synergetic therapy has emerged as a promising tumor elimination strategy.However,the low intracellular Fenton level and accumulation of therapeutics at the lesion site greatly limit the efficacy of ferroptosis therapy.To overcome these two bottlenecks,an inhalable metal polyphenol network(MPN)-hybrid liposome,encoded as LDG,was proposed for enhancing the intracellular Fenton reaction level by co-delivering the ferroptosis inducer dihydroartemisinin(DHA)and the ferrous ion(Fe2+)donor MPN.The synthesized LDG had excellent nebulization performance which significantly improved the accumulation in the lungs,about 8.2 times of intravenous injection.In terms of anticancer mechanisms,MPN raised the intracellular level of Fe2+by constructing iron cycling in the weakly acidic environment of tumors.Triggered by Fe2+,DHA with peroxide-bridge structure underwent a high level of Fenton-like reaction,promoted the production of intracellular reactive oxygen species(ROS)and induced strong ferroptosis while cooperating with apoptosis.LDG exhibited extraordinary antitumor ability in an orthotopic lung tumor model,whose tumor inhibition efficiency was 1.53(P=0.0014)and 1.32(P=0.0183)times of the LG group(liposomes coated with gallic acid(GA)-Fe MPN)and LD group(liposomes loaded with DHA),respectively,showing the strongest anticancer effect.In conclusion,the constructed MPN-hybrid liposomes could be a potent custom nanoplatform for pulmonary delivery and underscored the great potential of ferroptosis-apoptosis synergetic therapy.
