Intraocular lens(IOL)is a crucial implant for cataract therapy.Posterior capsule opacification(PCO)is the most common post-operative complication after IOL implantation,which is the abnormal hyperplasia of the residua...Intraocular lens(IOL)is a crucial implant for cataract therapy.Posterior capsule opacification(PCO)is the most common post-operative complication after IOL implantation,which is the abnormal hyperplasia of the residual lens epithelial cells(LECs)after IOL implantation in cataract surgery.It is reported that the cellular microenvironment in the lens capsule changes after surgery,such as the elevated secretion of matrix metalloproteinases(MMPs)and a decrease in pH due to undesired cell proliferation.In this study,MMP-2and pH-triggered drug delivery polysaccharide multilayer coating was designed and introduced onto the IOL surface for obtaining the cellular microenvironment-sensitive drug-eluting intraocular implant.The methacrylated heparin(HEP-MA)was synthesized and used to layer-by-layer self-assemble with the doxorubicin-loaded chitosan nanoparticles on the IOL surface.The matrix metalloproteinase-2(MMP-2)sensitive peptide with cysteine contained in both ends(GCRD-GPQGIWGQ-DRCG)was then used to crosslink the polysaccharide multilayer via the Michael addition reaction between sulfhydryl group in cysteines and double bonds in methacrylate groups.The multilayer construction and subsequent cross-linking were validated through ultraviolet-visible spectrophotometer(UV-Vis)and Fourier transform infrared spectroscopy(FTIR).After modification,the IOL material surface becomes more hydrophilic while the optical properties were well maintained.The MMP-2 and pH-sensitive drug sustained-release coating were successfully obtained on the IOL surface via such design.The enzyme-triggered cell proliferation inhibition was realized in the in vitro experiments.In an animal model,significant up-regulation of MMP-2 was observed in the aqueous humor after cataract surgery.The multi-functionalized polysaccharide-coated IOL implanted in the animal eye via cataract surgery effectively inhibits PCO formation while it keeps good in viuo biosafety.展开更多
Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the caps...Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the capsule bag.Although the surface modification and drug loading of intraocular lens(IOLs)have been effective in preventing PCO to some extent,the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application.In this study,we used non-viral gene delivery systems in combination with layer-by-layer(LBL)self-assembly technology,and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α(PDGFR-α).Herein,the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol)to form gene complexes.Gene complexes were characterized by dynamic light scattering,transmission electron microscopy(TEM)and agarose gel electrophoresis,and evaluated for storage and serum stability.The layer assembly behavior of the IOL surface,changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance,UV-vis,contact angle and TEM.In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect,and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors,as well as effective inhibition of PDGFR-αexpression and its mediated EMT process.The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes.This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.展开更多
Mineral compositions of aerosol particles were investigated at four sites （Aksu, Dunhuang, Zhenbeitai, and Tongliao） in desert regions of northern China from March to May in 2001 and 2002 during the intensive field ...Mineral compositions of aerosol particles were investigated at four sites （Aksu, Dunhuang, Zhenbeitai, and Tongliao） in desert regions of northern China from March to May in 2001 and 2002 during the intensive field campaign period of ACE-Asia （Aerosol Characterization Experiments-Asia）. The X-ray diffraction （XRD） results show the main minerals for Asian dust are illite, chlorite, kaolinite, quartz, feldspar, calcite, and dolomite. Gypsum, hornblende, and halite are also detected in several samples. Semi-quantitative mineralogical data of aerosol samples show that carbonate content decreases from western to eastern source areas; that is, soil dust collected at western source area sites of Dunhuang and Aksu are enriched with carbonate, while northeastern source area site of Tongliao is associated with low carbonate content. But the spatial distribution of feldspar exhibits a different pattern as compared to carbonate, increasing from the western to the eastern sources. The total clay content is significantly higher （73% in average） at the deposition site of Changwu than those at source areas. Air-mass back trajectory studies for the three dust storm events observed at Changwu, showed that soil dust transport pathways were as expected from carbonate content for the source identification, further demonstrating that carbonate was a useful tracer for eolian dust on regional scale in northern China.展开更多
Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery.However,the current intraocular lens(IOL)implanted after cataract surgery neither can adjust focal length in...Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery.However,the current intraocular lens(IOL)implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications.Herein,a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable,in situ curable,and adjustable IOL(FHTAB IOL).The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA,combined with BP NS,TA,and Ag NPs.FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation.The designed injectable FHTAB IOL possesses high transparency and transmittance,with a refractive index similar to the natural lens and adjustable properties.It was stabilized as a refractive medium without any leakage in the eye.In addition,the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo.This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.展开更多
基金financially supported by the Zhejiang Provincial Natural Science Foundation[LR23H180001]the Medical&Health Technology Program of Zhejiang Province[2022KY906].
文摘Intraocular lens(IOL)is a crucial implant for cataract therapy.Posterior capsule opacification(PCO)is the most common post-operative complication after IOL implantation,which is the abnormal hyperplasia of the residual lens epithelial cells(LECs)after IOL implantation in cataract surgery.It is reported that the cellular microenvironment in the lens capsule changes after surgery,such as the elevated secretion of matrix metalloproteinases(MMPs)and a decrease in pH due to undesired cell proliferation.In this study,MMP-2and pH-triggered drug delivery polysaccharide multilayer coating was designed and introduced onto the IOL surface for obtaining the cellular microenvironment-sensitive drug-eluting intraocular implant.The methacrylated heparin(HEP-MA)was synthesized and used to layer-by-layer self-assemble with the doxorubicin-loaded chitosan nanoparticles on the IOL surface.The matrix metalloproteinase-2(MMP-2)sensitive peptide with cysteine contained in both ends(GCRD-GPQGIWGQ-DRCG)was then used to crosslink the polysaccharide multilayer via the Michael addition reaction between sulfhydryl group in cysteines and double bonds in methacrylate groups.The multilayer construction and subsequent cross-linking were validated through ultraviolet-visible spectrophotometer(UV-Vis)and Fourier transform infrared spectroscopy(FTIR).After modification,the IOL material surface becomes more hydrophilic while the optical properties were well maintained.The MMP-2 and pH-sensitive drug sustained-release coating were successfully obtained on the IOL surface via such design.The enzyme-triggered cell proliferation inhibition was realized in the in vitro experiments.In an animal model,significant up-regulation of MMP-2 was observed in the aqueous humor after cataract surgery.The multi-functionalized polysaccharide-coated IOL implanted in the animal eye via cataract surgery effectively inhibits PCO formation while it keeps good in viuo biosafety.
基金supported by the Zhejiang Provincial Natural Science Foundation(LR23H180001)the Key Scientific and Technological Innovation Projects in Wenzhou(ZY2021002)+1 种基金Medical&Health Technology Program of Zhejiang Province(2022RC051)the Zhejiang Science and Technology Program of Traditional Chinese Medicine(2022ZB220).
文摘Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the capsule bag.Although the surface modification and drug loading of intraocular lens(IOLs)have been effective in preventing PCO to some extent,the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application.In this study,we used non-viral gene delivery systems in combination with layer-by-layer(LBL)self-assembly technology,and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α(PDGFR-α).Herein,the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol)to form gene complexes.Gene complexes were characterized by dynamic light scattering,transmission electron microscopy(TEM)and agarose gel electrophoresis,and evaluated for storage and serum stability.The layer assembly behavior of the IOL surface,changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance,UV-vis,contact angle and TEM.In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect,and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors,as well as effective inhibition of PDGFR-αexpression and its mediated EMT process.The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes.This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.
基金supported by the National Natural Science Foundation of China (Grants 40405023,40675081,and 40599422)a grant from SKLLQG,CASthe staff of Shaanxi Institute of Desert Research,and Aksu Water Balance Observatory of the Chinese Academy of Sciences for their support during sampling
文摘Mineral compositions of aerosol particles were investigated at four sites （Aksu, Dunhuang, Zhenbeitai, and Tongliao） in desert regions of northern China from March to May in 2001 and 2002 during the intensive field campaign period of ACE-Asia （Aerosol Characterization Experiments-Asia）. The X-ray diffraction （XRD） results show the main minerals for Asian dust are illite, chlorite, kaolinite, quartz, feldspar, calcite, and dolomite. Gypsum, hornblende, and halite are also detected in several samples. Semi-quantitative mineralogical data of aerosol samples show that carbonate content decreases from western to eastern source areas; that is, soil dust collected at western source area sites of Dunhuang and Aksu are enriched with carbonate, while northeastern source area site of Tongliao is associated with low carbonate content. But the spatial distribution of feldspar exhibits a different pattern as compared to carbonate, increasing from the western to the eastern sources. The total clay content is significantly higher （73% in average） at the deposition site of Changwu than those at source areas. Air-mass back trajectory studies for the three dust storm events observed at Changwu, showed that soil dust transport pathways were as expected from carbonate content for the source identification, further demonstrating that carbonate was a useful tracer for eolian dust on regional scale in northern China.
基金Zhejiang Provincial Natural Science Foundation[LR23H180001]Key Scientific and Technological Innovation Projects in Wenzhou[ZY2021002].
文摘Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery.However,the current intraocular lens(IOL)implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications.Herein,a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable,in situ curable,and adjustable IOL(FHTAB IOL).The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA,combined with BP NS,TA,and Ag NPs.FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation.The designed injectable FHTAB IOL possesses high transparency and transmittance,with a refractive index similar to the natural lens and adjustable properties.It was stabilized as a refractive medium without any leakage in the eye.In addition,the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo.This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.
