Artemisinin and its derivatives have emerged as promising therapeutic agents for cancer therapy by endogenous iron-mediated generation of free radicals.However,the enhanced antioxidant defense systems in cancer cells ...Artemisinin and its derivatives have emerged as promising therapeutic agents for cancer therapy by endogenous iron-mediated generation of free radicals.However,the enhanced antioxidant defense systems in cancer cells provide them with resistance to oxidative damage,greatly antagonizing the therapeutic efficacy that relies on inducing oxidative stress.Herein,a metal-organic framework(MOF)-based nanoplatform(CMD)is constructed to disrupt the cellular redox homeostasis and selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy.In cancer cells,the copper(II)sites in the MOF nanocarrier of CMD can efficiently weaken the cellular antioxidant capacity by depleting the overexpressed glutathione,simultaneously leading to the decomposition of the framework structure and the release of the encapsulated dihydroartemisinin.As a result,the damaged antioxidant defense system of cancer cells reduces its effect on oxidative stress alleviation and strengthens the therapeutic efficacy of dihydroartemisinin.On contrast,the low concentration of cellular glutathione in normal cells protects them from dihydroartemisinin-induced cytotoxicity by decelerating the drug release.In vivo results demonstrate that CMD could completely suppress the tumor growth in mice and show no evidence of toxicity,providing an effective strategy for the practical usage of dihydroartemisinin in cancer therapy.展开更多
The applicability of G-quadruplexes(G4s)as antiviral targets,therapeutic agents and diagnostic tools for coronavirus disease 2019(COVID-19)is currently being evaluated,which has drawn the extensive attention of the sc...The applicability of G-quadruplexes(G4s)as antiviral targets,therapeutic agents and diagnostic tools for coronavirus disease 2019(COVID-19)is currently being evaluated,which has drawn the extensive attention of the scientific community.During the COVID-19 pandemic,research in this field is rapidly accumulating.In this review,we summarize the latest achievements and breakthroughs in the use of G4s as antiviral targets,therapeutic agents and diagnostic tools for COVID-19,particularly using G4 ligands.Finally,strength and weakness regarding G4s in anti-SARS-CoV-2 field are highlighted for prospective future projects.展开更多
Artificial enzymes have provided great antimicrobial activity to combat wound infection.However,the lack of tissue repair capability compromised their treatment effect.Therefore,development of novel artificial enzyme ...Artificial enzymes have provided great antimicrobial activity to combat wound infection.However,the lack of tissue repair capability compromised their treatment effect.Therefore,development of novel artificial enzyme concurrently with the excellent antibacterial activity and the property of promoting wound healing are required.Here,we demonstrated the hydrogel-based artificial enzyme composed of copper and amino acids possessed intrinsic peroxidase-like catalytic activity,which could combat wound pathogen effectively and accelerate wound healing by stimulating angiogenesis and collagen deposition.Furthermore,the system possesses good biocompatibility for practical application.The synergic effect of the hydrogel-based artificial enzyme promises the system as a new paradigm in bacteria-infected wound healing therapy.展开更多
Metal ions are involved in Aβ aggregate deposition and neurotoxicity via various processes, including acceleration of Aβ aggregation, disruption of normal metal homeostasis, and formation of reactive oxygen species ...Metal ions are involved in Aβ aggregate deposition and neurotoxicity via various processes, including acceleration of Aβ aggregation, disruption of normal metal homeostasis, and formation of reactive oxygen species （ROS）. Although metal chelation is a promising therapeutic strategy for Alzheimer＇s disease （AD）, the widespread use of chelation therapy faces a significant problem; namely, it is difficult to differentiate toxic metals associated with Aβ plaques from those required by normal metal homeostasis. Furthermore, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration also restrict AD treatment through a single therapeutic strategy. This paper presents a novel bifunctional platform by integrating nonpharmacological and pharmacological cues into one system for AD treatment. This electrically responsive drug release platform, based on conducting polymer polypyrrole （PPy） incorporated with graphene-mesoporous silica nanohybrids （GSN） nanoreserviors, could realize on-demand controlled drug delivery with spatial and temporal control. Electrochemical stimulation can treat peripheral nerve injury （PNI） to stimulate neurite outgrowth. This novel system can also effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ-related toxicity. The purpose of this research is to promote the design of noninvasive remote-controlled multifunctional systems for AD treatment.展开更多
We report a new strategy for improving the efficiency of non-specific amyloidosis therapeutic drugs by coating amyloid-responsive lipid bilayers. The approach had drawn inspiration from amyloid oligomer-mediated cell...We report a new strategy for improving the efficiency of non-specific amyloidosis therapeutic drugs by coating amyloid-responsive lipid bilayers. The approach had drawn inspiration from amyloid oligomer-mediated cell membrane disruption in the pathogenesis of amyloidosis. A graphene-mesoporous silica hybrid （GMS）-supported lipid bilayer （GMS-Lip） system was used as a drug carrier, Drugs were well confined inside the nanocarrier until encountering amyloid oligomers, which could pierce the lipid bilayer coat and cause drug release. To ensure release efficiency, use of a near-infrared （NIR） laser was also introduced to facilitate drug release, taking advantage of the photothermal effect of GMS and thermal sensitivity of lipid bilayers. To facilitate tracking, fluorescent dyes were co-loaded with drugs within GMS-Lip and the NIR laser was used once the oligomer-triggered release had been signaled. Because of the spatially and temporally controllable property of light, the NIR-assisted release could be easily and selectively activated locally by tracking the fluorescence signal. Our design is based on arnyloidosis pathogenesis, the cytotoxic amyloid oligomer self-triggered release via cell membrane disruption, for the controlled release of drug molecules. The results may shed light on the development of pathogenesis- inspired drug delivery systems,展开更多
Nitric oxide(NO)gas therapy,especially,L-arginine(L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy.However,current strategies are unable to differentiate well between...Nitric oxide(NO)gas therapy,especially,L-arginine(L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy.However,current strategies are unable to differentiate well between normal cells and cancer cells,which may lead to unpredictable toxicity.Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase(NOS),herein,a nanozyme-based NO generator,cerium oxide(CeO_(2))-AT,is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment.In this system,after being endocytosed into cancer cells,the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells,which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis.In addition,the generator with catalase(CAT)-like activity can catalyze H_(2)O_(2)to produce O_(2),which can promote the generation of NO and improve the performance of NO gas therapy.What is more,our system has no obvious impact on the viability of normal cells owing to the less production of NO.Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.展开更多
Accurate regulation of cellular zinc signaling is imperative to decipher underlyingzinc functions and develop new therapeutic agents. However, the ability tomodulate zinc in a spatiotemporal manner remains elusive. We...Accurate regulation of cellular zinc signaling is imperative to decipher underlyingzinc functions and develop new therapeutic agents. However, the ability tomodulate zinc in a spatiotemporal manner remains elusive. We herein report anintelligent spiropyran-upconversion （SP-UCNPs） based nanosystem that enablesnear-infrared （NIR） light-controlled zinc release at precise times and locations.The magnitude of zinc release can be simply manipulated by varying the durationof NIR irradiation. Moreover, the utilization of NIR light not only showed littledamage to cells but also significantly improved penetration depth. By evaluatingactivity of a model protein, phosphatase 2A, we further validated zinc signalingactivation. Importantly, our strategy may be broadly applicable to other types ofmetal ions, like the ubiquitous second messenger calcium. More importantly, ourstrategy can potentially enable the precise control of specific signaling pathways ofmetal ions while minimizing cellular damage, facilitating the advanced manipulationof cellular dynamics.展开更多
The biological functions of amyloid β(Aβ)peptides have received much attention,playing a central role in the pathogenesis of Alzheimer’s disease(AD).Recent studies have demonstrated that AD is asso-ciated with canc...The biological functions of amyloid β(Aβ)peptides have received much attention,playing a central role in the pathogenesis of Alzheimer’s disease(AD).Recent studies have demonstrated that AD is asso-ciated with cancer.However,it is still unknown if there is a correlation between Aβand cancer.展开更多
基金the Program of Science and Technology Development Plan of Jilin Province of China(No.20200201099JC)the National Natural Science Foundation of China(Nos.21871249 and 22105197).
文摘Artemisinin and its derivatives have emerged as promising therapeutic agents for cancer therapy by endogenous iron-mediated generation of free radicals.However,the enhanced antioxidant defense systems in cancer cells provide them with resistance to oxidative damage,greatly antagonizing the therapeutic efficacy that relies on inducing oxidative stress.Herein,a metal-organic framework(MOF)-based nanoplatform(CMD)is constructed to disrupt the cellular redox homeostasis and selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy.In cancer cells,the copper(II)sites in the MOF nanocarrier of CMD can efficiently weaken the cellular antioxidant capacity by depleting the overexpressed glutathione,simultaneously leading to the decomposition of the framework structure and the release of the encapsulated dihydroartemisinin.As a result,the damaged antioxidant defense system of cancer cells reduces its effect on oxidative stress alleviation and strengthens the therapeutic efficacy of dihydroartemisinin.On contrast,the low concentration of cellular glutathione in normal cells protects them from dihydroartemisinin-induced cytotoxicity by decelerating the drug release.In vivo results demonstrate that CMD could completely suppress the tumor growth in mice and show no evidence of toxicity,providing an effective strategy for the practical usage of dihydroartemisinin in cancer therapy.
基金Financial support was provided by the National Key R&D Program of China(2019YFA0709202)the National Natural Science Foundation of China(91856205,21820102009,22237006,22107098,22122704)the Key Program of Frontier of Sciences(CAS QYZDJ-SSW-SLHO52).
文摘The applicability of G-quadruplexes(G4s)as antiviral targets,therapeutic agents and diagnostic tools for coronavirus disease 2019(COVID-19)is currently being evaluated,which has drawn the extensive attention of the scientific community.During the COVID-19 pandemic,research in this field is rapidly accumulating.In this review,we summarize the latest achievements and breakthroughs in the use of G4s as antiviral targets,therapeutic agents and diagnostic tools for COVID-19,particularly using G4 ligands.Finally,strength and weakness regarding G4s in anti-SARS-CoV-2 field are highlighted for prospective future projects.
基金This project was supported by the 973 Project （No. 2011CB936004）, the National Natural Science Foundation of China （NSFC） （Nos. 20831003, 90813001, 20833006, and 90913007） and Funds from the Chinese Academy of Sciences.
基金This work was supported by the National Basic Research Program of China （Nos. 2011CB936004 and 2012CB720602） and the National Natural Science Foundation of China （Nos. 21210002, 21431007, 91413111, 21402183）.
基金Financial support was provided by the National Basic Research Program of China （973 Project） （Nos. 2011CB936004 and 2012CB720602） and the National Natural Science Foundation of China （Nos. 21210002, 21431007, 21402183, and 21533008）.
基金Financial support was provided by the National Natural Science Foundation of China(Nos.21871249,21673223,21977091,21431007,21533008,and 21820102009)the Key Program of Frontier of Sciences,CAS QYZDJ-SSW-SLH052.
文摘Artificial enzymes have provided great antimicrobial activity to combat wound infection.However,the lack of tissue repair capability compromised their treatment effect.Therefore,development of novel artificial enzyme concurrently with the excellent antibacterial activity and the property of promoting wound healing are required.Here,we demonstrated the hydrogel-based artificial enzyme composed of copper and amino acids possessed intrinsic peroxidase-like catalytic activity,which could combat wound pathogen effectively and accelerate wound healing by stimulating angiogenesis and collagen deposition.Furthermore,the system possesses good biocompatibility for practical application.The synergic effect of the hydrogel-based artificial enzyme promises the system as a new paradigm in bacteria-infected wound healing therapy.
基金This work was supported by the National Basic Research Program of China （Nos. 2012CB720602 and 2011CB936004）, and the National Natural Science Foundation of China （Nos. 21210002, 21431007, and 21533008）.
文摘淀粉的肽(A) 聚集是在 Alzheimers 疾病(广告) 的致病的关键步。生产的抑制， A 的存在总数和清理的溶解对广告代表有效治疗学的策略。此处，新奇的铂(II ) 协调了 graphitic 碳氮化物(g-C <sub>3</sub > N <sub>4</sub>) nanosheet (g-C <sub>3</sub > N <sub>4</sub>@Pt) 被设计了 covalently 绑在 A 并且调制肽聚集和毒性。而且， g-C <sub>3</sub > N <sub>4</sub>@Pt nanosheets 拥有高 photocatalytic 活动并且能氧化在可见轻照耀之上的 A，显著地 attenuating 聚集力量和 A 的 neurotoxicity。由于它穿过血大脑障碍(BBB ) 和它的好 biocompatibility 的能力， g-C <sub>3</sub > N <sub>4</sub>@Pt nanosheet 是聚集的一个有希望的禁止者。这研究可以为为广告的处理使用的新奇多功能的 nanomaterials 的工程担任一个模型。
基金support from the National Natural Science Foundation of China （Nos. 21210002, 21431007, 21533008, 21403209, 21601175, and 21673223） and the Jilin Province Science and Technology Develop- ment Plan Project （No. 20140101039JC）.
文摘Metal ions are involved in Aβ aggregate deposition and neurotoxicity via various processes, including acceleration of Aβ aggregation, disruption of normal metal homeostasis, and formation of reactive oxygen species （ROS）. Although metal chelation is a promising therapeutic strategy for Alzheimer＇s disease （AD）, the widespread use of chelation therapy faces a significant problem; namely, it is difficult to differentiate toxic metals associated with Aβ plaques from those required by normal metal homeostasis. Furthermore, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration also restrict AD treatment through a single therapeutic strategy. This paper presents a novel bifunctional platform by integrating nonpharmacological and pharmacological cues into one system for AD treatment. This electrically responsive drug release platform, based on conducting polymer polypyrrole （PPy） incorporated with graphene-mesoporous silica nanohybrids （GSN） nanoreserviors, could realize on-demand controlled drug delivery with spatial and temporal control. Electrochemical stimulation can treat peripheral nerve injury （PNI） to stimulate neurite outgrowth. This novel system can also effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ-related toxicity. The purpose of this research is to promote the design of noninvasive remote-controlled multifunctional systems for AD treatment.
基金Financial support was provided by the National Basic Research Program of China （973 Program） （No. 2012CB720602）, the Project of Science and Technology Development Plan for Jilin Province （No. 20150520004JH） and the National Natural Science Foundation of China （NSFC） （Nos. 21210002, 21431007, 21402183 and 21533008）.
基金This work was supported by the National Basic Research Program of China （Nos. 2011CB936004 and 2012CB720602）, and the National Natural Science Foundation of China （Nos. 21210002, 21431007, 91413111, and 21401187）.
文摘We report a new strategy for improving the efficiency of non-specific amyloidosis therapeutic drugs by coating amyloid-responsive lipid bilayers. The approach had drawn inspiration from amyloid oligomer-mediated cell membrane disruption in the pathogenesis of amyloidosis. A graphene-mesoporous silica hybrid （GMS）-supported lipid bilayer （GMS-Lip） system was used as a drug carrier, Drugs were well confined inside the nanocarrier until encountering amyloid oligomers, which could pierce the lipid bilayer coat and cause drug release. To ensure release efficiency, use of a near-infrared （NIR） laser was also introduced to facilitate drug release, taking advantage of the photothermal effect of GMS and thermal sensitivity of lipid bilayers. To facilitate tracking, fluorescent dyes were co-loaded with drugs within GMS-Lip and the NIR laser was used once the oligomer-triggered release had been signaled. Because of the spatially and temporally controllable property of light, the NIR-assisted release could be easily and selectively activated locally by tracking the fluorescence signal. Our design is based on arnyloidosis pathogenesis, the cytotoxic amyloid oligomer self-triggered release via cell membrane disruption, for the controlled release of drug molecules. The results may shed light on the development of pathogenesis- inspired drug delivery systems,
基金supported by the National Key R&D Program of China(No.2021YFF1200701)the National Natural Science Foundation of China(Nos.91856205,21820102009,and 21871249)the Key Program of Frontier of Sciences(No.CAS QYZDJ-SSW-SLH052)。
文摘Nitric oxide(NO)gas therapy,especially,L-arginine(L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy.However,current strategies are unable to differentiate well between normal cells and cancer cells,which may lead to unpredictable toxicity.Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase(NOS),herein,a nanozyme-based NO generator,cerium oxide(CeO_(2))-AT,is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment.In this system,after being endocytosed into cancer cells,the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells,which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis.In addition,the generator with catalase(CAT)-like activity can catalyze H_(2)O_(2)to produce O_(2),which can promote the generation of NO and improve the performance of NO gas therapy.What is more,our system has no obvious impact on the viability of normal cells owing to the less production of NO.Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.
文摘Accurate regulation of cellular zinc signaling is imperative to decipher underlyingzinc functions and develop new therapeutic agents. However, the ability tomodulate zinc in a spatiotemporal manner remains elusive. We herein report anintelligent spiropyran-upconversion （SP-UCNPs） based nanosystem that enablesnear-infrared （NIR） light-controlled zinc release at precise times and locations.The magnitude of zinc release can be simply manipulated by varying the durationof NIR irradiation. Moreover, the utilization of NIR light not only showed littledamage to cells but also significantly improved penetration depth. By evaluatingactivity of a model protein, phosphatase 2A, we further validated zinc signalingactivation. Importantly, our strategy may be broadly applicable to other types ofmetal ions, like the ubiquitous second messenger calcium. More importantly, ourstrategy can potentially enable the precise control of specific signaling pathways ofmetal ions while minimizing cellular damage, facilitating the advanced manipulationof cellular dynamics.
基金This work was supported by the National Natural Science Foundation(NSFC,21431007,21533008,21820102009,91856205,21871249,and 21807096)Key Program of Frontier of Sciences(CAS QYZDJ-SSW-SLH052),China.
文摘The biological functions of amyloid β(Aβ)peptides have received much attention,playing a central role in the pathogenesis of Alzheimer’s disease(AD).Recent studies have demonstrated that AD is asso-ciated with cancer.However,it is still unknown if there is a correlation between Aβand cancer.
