The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(...The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model;moreover, NLRP3 inflammasome activation(NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus(NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species(mt ROS)production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mt ROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.展开更多
Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of s...Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by Chinese researchers in this field,with emphasis on those reported in the past five years.展开更多
Drug loading capacity is very important in the construction of targeted drug delivery systems(TDDSs)for the improvement of drug delivery efficiency.However,the drug-loading capacity of most nanomaterials is non-ideali...Drug loading capacity is very important in the construction of targeted drug delivery systems(TDDSs)for the improvement of drug delivery efficiency.However,the drug-loading capacity of most nanomaterials is non-idealistic,and developing the high drug-loading TDDSs is still a critical challenge.In this work,an ultrahigh loading system(denoted as HMPB_(2))was prepared via J-aggregation of an aza-boron dipyrromethene derivative(Bod)by using hollow MnO_(2)modified with glucosamine pillar[5]arene as a carrier,which was demonstrated to have typical J-aggregate absorption of Bod,specific cancer cells targeting ability,negligible dark cytotoxicity,and potent phototoxicity.This work provides a successful example to construct an ultrahigh drug-loading system via J-aggregation for targeted delivery.展开更多
Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple mo...Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple modes often makes the composition of the system more complex,which is not conducive to clinical application.In this study,a dual phototherapy ligand carboxyl-modified Aza-BODIPY(BOD-COOH)and metal active center Cu^(2+)were used to construct multiple-modes metalphotosensitizer nanoparticles(BOD-Cu NPs)via one-step coordination self-assembly for combination therapy of CDT/PDT/PTT.In order to improve delivery efficiency,the targeted hydrophilic molecule pyridinemodified glucose derivative(G-Py)was synthesized and coated onto the BOD-Cu NPs to form a glycosylated nano metal-photosensitizer BOD-Cu@G by electrostatic interaction.The Cu^(2+)in BOD-Cu@G could not only be used as a coordination node for metal-driven self-assembly but also consume intracellular glutathione(GSH),and then catalyze Fenton-like reaction to generate hydroxyl radical(·OH)for CDT.In vitro and in vivo studies revealed that BOD-Cu@G could achieve excellent anti-tumor efficiency by CDTenhanced dual phototherapy.展开更多
Nano-drug delivery systems with multiple stimulus-responsive capabilities have superior response performance and efficient drug release.Nevertheless,it is sophisticated to construct multiple stimulus-responsive system...Nano-drug delivery systems with multiple stimulus-responsive capabilities have superior response performance and efficient drug release.Nevertheless,it is sophisticated to construct multiple stimulus-responsive systems where the two or more functional groups need to be introduced simultaneously.Xanthate,one functional group with pH and H2O2 stimulus responsiveness,has significant potential applications for building dual-responsive drug delivery system.Herein,we present a novel dual stimuli-responsive supramolecular drug delivery system by using sodium xanthate derivative(SXD)as guest molecule and quaternary ammonium capped pillar[5]arene(QAP5)as host molecule through host-guest interaction on the basis of electrostatic interaction.The amphiphile QAP5⊃SXD could self-assemble into vesicles to efficiently load the anti-cancer drug DOX.The experimental results showed that QAP5⊃SXD nanoparticles could achieve efficient drug delivery and controlled release in the tumor microenvironment.Cytotoxicity experiments proved that DOX@QAP5⊃SXD nanoparticles could significantly improve the anticancer efficiency of free DOX on cancer cells.The present study provides an efficient strategy to develop supramolecular nanocarriers with dual-responsiveness in one functional group for controlled drug release.展开更多
A novel approach for fabricating branched-chain (BC) carbohydrate chips to study carbohydrate-protein interactions using Quartz Crystal Microbalance (QCM) biosensor was developed. This approach utilizes functional...A novel approach for fabricating branched-chain (BC) carbohydrate chips to study carbohydrate-protein interactions using Quartz Crystal Microbalance (QCM) biosensor was developed. This approach utilizes functional alkynyl-branch molecule modified chip surfaces, which through the terminal alkynyl group for covalent linking of unprotected azide-carbohydrates. The unprotected azide-carbohydrates were syhthesized in one-step using 2-azido-l,B-dimethylqmidazolinium as catalyst, avoiding complex chemical modifications. Additionally, the branch surface modified with the carbohydrates not only supplies more specific binding site but also reveals significant cluster effect. To exemplify the sugar cluster effect on BC carbohydrate chips, BC Galactose and Mannose chips prepared in this work were used to determine carbohydrate-lectin interactions using QCM biosensor. The results clearly showed that BC chip significantly improves the detection sensitivity compared with the straight-chain (SC) chip. More importantly, the BC galactose chip sensitivity was enhanced 40% compared with the SC galactose chip.展开更多
Acrylamide copolymers are often used as acidizing diverting and thickening agents for their advantageous thickening,flocculation,adhesion and resistance reduction properties.Experimental results indicate that the acid...Acrylamide copolymers are often used as acidizing diverting and thickening agents for their advantageous thickening,flocculation,adhesion and resistance reduction properties.Experimental results indicate that the acid concentration greatly affects the properties of acrylamide polymers,which varies from results reported by other researchers.Considering the theoretical and field application value of the present study,four comparable acrylamide-based polymers were synthesized,and their macro-and micro-changes as well as the related changes in viscosity and molecular weight were studied in high-concentration hydrochloric acid.A proposed mechanism of acrylamide copolymer stability and degradation is provided,and further suggestions are made for the modification of acrylamide copolymers.展开更多
基金supported by grants from the Natural Science Foundation of Guangdong Province (Grant no: 2017A030313670)the National Natural Science Foundation of China (81572175 and 81772386)。
文摘The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model;moreover, NLRP3 inflammasome activation(NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus(NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species(mt ROS)production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mt ROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.
文摘Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by Chinese researchers in this field,with emphasis on those reported in the past five years.
基金the National Natural Science Foundation of China(Nos.22171230 and 21877088)the Project of Science and Technology of Social Development in Shaanxi Province(No.2021SF-120)。
文摘Drug loading capacity is very important in the construction of targeted drug delivery systems(TDDSs)for the improvement of drug delivery efficiency.However,the drug-loading capacity of most nanomaterials is non-idealistic,and developing the high drug-loading TDDSs is still a critical challenge.In this work,an ultrahigh loading system(denoted as HMPB_(2))was prepared via J-aggregation of an aza-boron dipyrromethene derivative(Bod)by using hollow MnO_(2)modified with glucosamine pillar[5]arene as a carrier,which was demonstrated to have typical J-aggregate absorption of Bod,specific cancer cells targeting ability,negligible dark cytotoxicity,and potent phototoxicity.This work provides a successful example to construct an ultrahigh drug-loading system via J-aggregation for targeted delivery.
基金supported by the National Natural Science Foundation of China(No.22171230)the Project of Science and Technology of Social Development in Shaanxi Province(No.2023YBSF-151)。
文摘Chemodynamic therapy(CDT)combined with dual phototherapy(photothermal therapy(PTT)and photodynamic therapy(PDT))is an efficient way to synergistically improve anti-tumor efficacy.However,the combination of multiple modes often makes the composition of the system more complex,which is not conducive to clinical application.In this study,a dual phototherapy ligand carboxyl-modified Aza-BODIPY(BOD-COOH)and metal active center Cu^(2+)were used to construct multiple-modes metalphotosensitizer nanoparticles(BOD-Cu NPs)via one-step coordination self-assembly for combination therapy of CDT/PDT/PTT.In order to improve delivery efficiency,the targeted hydrophilic molecule pyridinemodified glucose derivative(G-Py)was synthesized and coated onto the BOD-Cu NPs to form a glycosylated nano metal-photosensitizer BOD-Cu@G by electrostatic interaction.The Cu^(2+)in BOD-Cu@G could not only be used as a coordination node for metal-driven self-assembly but also consume intracellular glutathione(GSH),and then catalyze Fenton-like reaction to generate hydroxyl radical(·OH)for CDT.In vitro and in vivo studies revealed that BOD-Cu@G could achieve excellent anti-tumor efficiency by CDTenhanced dual phototherapy.
基金supported by the National Natural Science Foundation of China(Nos.21877088.22171230)China Postdoctoral Science Foundation(No.2016M602861).
文摘Nano-drug delivery systems with multiple stimulus-responsive capabilities have superior response performance and efficient drug release.Nevertheless,it is sophisticated to construct multiple stimulus-responsive systems where the two or more functional groups need to be introduced simultaneously.Xanthate,one functional group with pH and H2O2 stimulus responsiveness,has significant potential applications for building dual-responsive drug delivery system.Herein,we present a novel dual stimuli-responsive supramolecular drug delivery system by using sodium xanthate derivative(SXD)as guest molecule and quaternary ammonium capped pillar[5]arene(QAP5)as host molecule through host-guest interaction on the basis of electrostatic interaction.The amphiphile QAP5⊃SXD could self-assemble into vesicles to efficiently load the anti-cancer drug DOX.The experimental results showed that QAP5⊃SXD nanoparticles could achieve efficient drug delivery and controlled release in the tumor microenvironment.Cytotoxicity experiments proved that DOX@QAP5⊃SXD nanoparticles could significantly improve the anticancer efficiency of free DOX on cancer cells.The present study provides an efficient strategy to develop supramolecular nanocarriers with dual-responsiveness in one functional group for controlled drug release.
基金the National Natural Science Foundation of China (Nos. 31270861 and 21572181)for financial support
文摘A novel approach for fabricating branched-chain (BC) carbohydrate chips to study carbohydrate-protein interactions using Quartz Crystal Microbalance (QCM) biosensor was developed. This approach utilizes functional alkynyl-branch molecule modified chip surfaces, which through the terminal alkynyl group for covalent linking of unprotected azide-carbohydrates. The unprotected azide-carbohydrates were syhthesized in one-step using 2-azido-l,B-dimethylqmidazolinium as catalyst, avoiding complex chemical modifications. Additionally, the branch surface modified with the carbohydrates not only supplies more specific binding site but also reveals significant cluster effect. To exemplify the sugar cluster effect on BC carbohydrate chips, BC Galactose and Mannose chips prepared in this work were used to determine carbohydrate-lectin interactions using QCM biosensor. The results clearly showed that BC chip significantly improves the detection sensitivity compared with the straight-chain (SC) chip. More importantly, the BC galactose chip sensitivity was enhanced 40% compared with the SC galactose chip.
文摘Acrylamide copolymers are often used as acidizing diverting and thickening agents for their advantageous thickening,flocculation,adhesion and resistance reduction properties.Experimental results indicate that the acid concentration greatly affects the properties of acrylamide polymers,which varies from results reported by other researchers.Considering the theoretical and field application value of the present study,four comparable acrylamide-based polymers were synthesized,and their macro-and micro-changes as well as the related changes in viscosity and molecular weight were studied in high-concentration hydrochloric acid.A proposed mechanism of acrylamide copolymer stability and degradation is provided,and further suggestions are made for the modification of acrylamide copolymers.