Combining cytotoxic drugs with tumor microenvironment(TME)modulator agents is an effective strategy to enhance anti-tumor effects.In this study,two natural anti-tumor active ingredients celastrol(CEL)and glycyrrhetini...Combining cytotoxic drugs with tumor microenvironment(TME)modulator agents is an effective strategy to enhance anti-tumor effects.In this study,two natural anti-tumor active ingredients celastrol(CEL)and glycyrrhetinic acid(GA)were combined for tumor treatment.In order to ensure the precise co-delivery and controllable synchronous release of combined drugs to tumors,it is necessary to construct a suitable nano-drug delivery platform.Based on this,we coupled hyaluronic acid(HA)with CEL by amide reaction to obtain an amphiphilic polymer prodrug HA-SS-CEL,and GA was spontaneously loaded into polymer micelles by self-assembly to obtain G/HSSC-M.G/HSSC-M has ideal size distribution,redox-responsive synchronous drug release,enhanced tumor cell internalization and in vivo tumor targeting.Compared with free drugs,the construction of multifunctional polymer micelles makes G/HSSC-M show better anticancer effect at the same concentration,and can significantly inhibit the proliferation and migration of HepG2 and 4T1 cells.In the in vivo experiments,G/HSSC-M achieved a tumor inhibition rate as high as 75.12%in H22 tumor-bearing mice.The mechanism included regulation of M1/M2 macrophage polarization,inhibition of Janus kinase 1/signal transducer and activator of transcription 3(JAK1/STAT3)signaling pathway,and remodeling of tumor blood vessels.Therefore,the development of prodrug micelles coloaded with CEL and GA provides a promising drug co-delivery strategy for combined cancer therapy.展开更多
Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNP...Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed legumain.The aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral retention.In vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain expression.In vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral injection.More importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 tumor.The effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.展开更多
The construction of oxide/metal composite catalysts is a competent means of exploiting the electronic interactions between oxide/metal to enhance catalytic activity.In this work,we construct a novel heterogeneous comp...The construction of oxide/metal composite catalysts is a competent means of exploiting the electronic interactions between oxide/metal to enhance catalytic activity.In this work,we construct a novel heterogeneous composite(Ru/HfO_(2)-NC)with Ru/HfO2nanoparticles nested in nitrogen-doped porous carbon via a zeolitic imidazole frameworks-assisted(ZIF)co-precipitation and calcination approach.In particular,ZIF guides an in-situ construction of nested configuration and confines the scattered nanoparticles.Strikingly,Ru/HfO_(2)-NC exhibits unusual ORR activity,superb durability,and methanol tolerance in0.1 M KOH solution with high half-wave potential(E1/2)of 0.83 V and follows a near-4e-reaction pathway.Additionally,the ZAB assembled with cathodic Ru/HfO_(2)-NC outputs a power density of 157.3 m W cm^(-2),a specific capacity of 775 mA h g-1Zn,and a prolonged lifespan of 258 h at 5 mA cm^(-2).Meanwhile,the catalyst has demonstrated potential applicability in flexible ZAB.As suggested by experimental results and density functional theory(DFT)analysis,the remarkable property possibly originated from the optimization of the adsorption and desorption of reactive intermediates caused by the reconfiguration of the electronic structure between Ru and HfO_(2).展开更多
Immunotherapy of tumor attracts great attention in the past several years attributing to the potential of completely erasing primary tumor and metastasis.Therefore,pharmaceutical companies developed many antibodies th...Immunotherapy of tumor attracts great attention in the past several years attributing to the potential of completely erasing primary tumor and metastasis.Therefore,pharmaceutical companies developed many antibodies that act as immune check point blockade(ICB),such as Nivolumab,Atezolizumab and Ipilimumab.展开更多
FeSO_(4) has the characteristics of low cost and theoretical high energy density(799 W·h·kg^(-1) with a two-electron reaction),which can meet the demand for next-generation lithium-ion batteries.Herein,FeSO_...FeSO_(4) has the characteristics of low cost and theoretical high energy density(799 W·h·kg^(-1) with a two-electron reaction),which can meet the demand for next-generation lithium-ion batteries.Herein,FeSO_(4) as a novel highperformance conversion-reaction type cathode is investigated.We use dopamine as a carbon coating source to increase its electronic conductivity.FeSO_(4)@C demonstrates a high reversible specific capacity(512 mA·h·g^(-1))and a superior cycling performance(482 mA·h·g^(-1) after 250 cycles).In addition,we further study its reaction mechanism.The FeSO_(4) is converted to Fe and Li2SO_(4) during lithium ion insertion and the Fe-Li_(2)SO_(4) grain boundaries further store additional lithium ions.Our findings are valuable in exploring other new conversion-type lithium ion battery cathodes.展开更多
Nanomedicines have revolutionized disease prevention,diagnosis,and treatment.Since the approval of Liposomal doxorubicin(Doxil)in 1995,various nanomedicines have been successfully developed1.Specifically,the COVID-19 ...Nanomedicines have revolutionized disease prevention,diagnosis,and treatment.Since the approval of Liposomal doxorubicin(Doxil)in 1995,various nanomedicines have been successfully developed1.Specifically,the COVID-19 pandemic highlighted the significance of nanomedicines,as lipid nanoparticles facilitated the mRNA vaccines success,thereby remarkable accelerating the development of RNA-drugs2,3.展开更多
Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity,which are uniquely driven by single-atom constructs.A dramatic increase in antioxidant capacity,158 times more than natural ...Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity,which are uniquely driven by single-atom constructs.A dramatic increase in antioxidant capacity,158 times more than natural trolox,is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au_(24)Cu_(1).Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis(OA),pH-dependent dendritic mesoporous silica nanoparticles(DMSNs)coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions,thereby enhancing the duration of effectiveness.Nonetheless,achieving high therapeutic efficacy remains a significant challenge.Herein,we describe the construction of a Clusterzymes-DMSNs-PEG complex(CDP)which remarkably diminishes reactive oxygen species(ROS)and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway.In the rabbit ACLT(anterior cruciate ligament transection)model,the CDP complex demonstrated inhibition of matrix metalloproteinase activity,preservation of type Ⅱ collagen and aggregation protein secretion,thus prolonging the clusterzymes’protective influence on joint cartilage structure.Our research underscores the efficacy of the CDP complex in ROS-scavenging,enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment,leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway.This study illuminates the design,composition,and use of DMSNs and clusterzymes in biomedicine,thus charting a promising course for the development of novel therapeutic strategies in alleviating OA.展开更多
Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency,nanoparticl...Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency,nanoparticles need to change size so as to fully utilize the enhanced permeability and retention(EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin(BSA) protected gold nanocluster(Au NC@CBSA,21.06 nm) to both load indocyanine green(ICG) and act as imaging probe to realize theranostic. Then Au NC@CBSA-ICG was fabricated with negatively charged hyaluronic acid(HA) to form Au NC@CBSAICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed Au NC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter in vitro or in vivo, Au NC@CBSAICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated Au NC@CBSA-ICG@HA was potential for breast cancer therapy.展开更多
As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to dev...As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.展开更多
Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention,which finally enhanced the a...Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention,which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6(Ce6), hydrophilic chemotherapeutic drug berberrubine(BBR) and matrix metalloproteinase-2(MMP-2) response peptide(PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6(BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine(PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively,we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.展开更多
In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M cells.The differentiation of M cells was induced by co-culture of...In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M cells.The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model.The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability.The differentiation of M cells was observed by upregulated expression of Sialyl Lewis A antigen(SLAA)and integrinβ1,and down-regulated activity of alkaline phosphatase.After targeting M cells with iRGD peptide(cRGDKGPDC),the transport of nanoparticles increased.In vivo,the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration.In the evaluation of immune effect in vivo,the nasal administration of OVA-PLGA/iRGD led to more release of IgG,IFN-γ,IL-2 and secretory IgA(sIgA)compared with OVA@PLGA group.Collectively,the study constructed in vitro M cell model,and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.展开更多
Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy.Herein,a kind of tumor cascade-targeted responsive liposome(NLG919@Lip-pep1)is develope...Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy.Herein,a kind of tumor cascade-targeted responsive liposome(NLG919@Lip-pep1)is developed by conjugating polypeptide inhibitor of PD-1 signal pathway(AUNP-12),which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2(MMP-2)cleavable peptide(GPLGVRGD).This targeted liposome is prepared through a mature preparation process,and indoleamine-2,3-dioxygenase(IDO)inhibitor NLG919 was encapsulated into it.Moreover,mediated by the enhanced permeability and retention effect(EPR effect)and AUNP-12,NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues.At the same time,the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12,thus realizing the precise block of PD-1 signal pathway,and restoring the activity of T cells.The exposure of secondary targeting moduleⅡVRGDC-NLG919@Lip mediated tumor cells targeting,and further relieved the immunosuppressive microenvironment.Overall,this study offers a potentially appealing paradigm of a high efficiency,low toxicity,and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer,which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.展开更多
Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly kill...Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.展开更多
Lithium(Li)metal is an ideal anode for the next generation high-energy-density batteries.However,it suffers from dendrite growth,side reactions,and infinite relative volume change.Effective strategies are using porous...Lithium(Li)metal is an ideal anode for the next generation high-energy-density batteries.However,it suffers from dendrite growth,side reactions,and infinite relative volume change.Effective strategies are using porous carbons or surface modification carbons to guide Li deposition into their pores.While the Li deposition behavior is still ambiguous.Here,we systematically determine their deposition behavior in various surface-modified carbons and in different electrolytes via optical microscopy and scanning electron microscopy study.It is found that Li will not spontaneously deposit into the carbon pores,which is significantly dependent on the carbon surface,current density,areal capacity,and electrolyte.Thus,a“lithiophilic”modified commercial hard carbon with Ag is developed as a stable“host”and efficient surface protection derived from the localized high-concentration electrolyte exhibits a pretty low volume change(5.3%)during cycling at a current density of 2 mA·cm^(−2)and an areal capacity of 2 mAh·cm^(−2).This strategy addresses the volume change and dendrite problems by rationally designed host and electrolyte,providing a broad perspective for realizing Li-metal anode.展开更多
Although drug delivery systems(DDS)are efficient in brain delivery,they face failure in clinical settings due to their potential toxicity to the central nervous system.Little is known about where the DDS will go after...Although drug delivery systems(DDS)are efficient in brain delivery,they face failure in clinical settings due to their potential toxicity to the central nervous system.Little is known about where the DDS will go after brain delivery,and no specific elimination route that shares a passage with DDS has been verified.Hence,identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation.In this study,we investigated nonreactive gold nanoclusters,which can deliver into the brain,to determine the elimination route of DDS.Subsequently,nanoclusters in the brain were systemically tracked and were found to be critically drained by the glymphatic system from the blood vessel basement membrane to periphery circulations(77.8±23.2%and 43.7±23.4%contribution).Furthermore,the nanoclusters could be actively transported across the blood-brain barrier(BBB)by exosomes(30.5±27.3%and 29.2±7.1%contribution).In addition,microglia promoted glymphatic drainage and passage across the BBB.The simultaneous work of the glymphatic system,BBB,and microglia revealed the fate of gold nanoclusters for brain delivery and provided a basis for further braindelivery DDS.展开更多
Impact Statement We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework(RDF)and implement a server to publish linked open data(LOD).As one ...Impact Statement We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework(RDF)and implement a server to publish linked open data(LOD).As one of the largest and most comprehensive semantic databases about coronaviruses,the resulted gcCov database demonstrates the capability of using data in the LOD framework to promote correlations between genotypes and phenotypes.These correlations will be helpful for future research on fundamental viral mechanisms and drug and vaccine designs.展开更多
基金supported by National Natural Science Foundation of China(No.81973662)National Interdisciplinary Innovation Team of Traditional Chinese Medicine(No.ZYYCXTDD-202209)+3 种基金Postdoctoral Fellowship Program of CPSF(No.GZC20230333)Sichuan Science and Technology Program(No.2023NSFSC1195)Central Guidance on Local Science and Technology Development Fund of Sichuan(No.23ZYZYTS0420)Central Nervous System Drug Key Laboratory of Sichuan Province(No.230046-01SZ).
文摘Combining cytotoxic drugs with tumor microenvironment(TME)modulator agents is an effective strategy to enhance anti-tumor effects.In this study,two natural anti-tumor active ingredients celastrol(CEL)and glycyrrhetinic acid(GA)were combined for tumor treatment.In order to ensure the precise co-delivery and controllable synchronous release of combined drugs to tumors,it is necessary to construct a suitable nano-drug delivery platform.Based on this,we coupled hyaluronic acid(HA)with CEL by amide reaction to obtain an amphiphilic polymer prodrug HA-SS-CEL,and GA was spontaneously loaded into polymer micelles by self-assembly to obtain G/HSSC-M.G/HSSC-M has ideal size distribution,redox-responsive synchronous drug release,enhanced tumor cell internalization and in vivo tumor targeting.Compared with free drugs,the construction of multifunctional polymer micelles makes G/HSSC-M show better anticancer effect at the same concentration,and can significantly inhibit the proliferation and migration of HepG2 and 4T1 cells.In the in vivo experiments,G/HSSC-M achieved a tumor inhibition rate as high as 75.12%in H22 tumor-bearing mice.The mechanism included regulation of M1/M2 macrophage polarization,inhibition of Janus kinase 1/signal transducer and activator of transcription 3(JAK1/STAT3)signaling pathway,and remodeling of tumor blood vessels.Therefore,the development of prodrug micelles coloaded with CEL and GA provides a promising drug co-delivery strategy for combined cancer therapy.
基金supported by the Beijing Natural Science Foundation(No.L222128)Beijing Institute of Technology Research Fund Program for Young Scholars(No.XSQD-202121010)National Natural Science Foundation of China(No.81961138009)。
文摘Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets.Herein,we proposed a legumain-triggered aggregable gold nanoparticle(GNP)delivery platform(GNPs-A&C).GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed legumain.The aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis,leading to enhanced intratumoral retention.In vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain expression.In vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs,regardless of intravenous or intratumoral injection.More importantly,this delivery platform significantly improved the chemotherapeutic effect of doxorubicin(DOX)towards subcutaneous xenograft C6 tumor.The effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.
基金supported by the National Natural Science Foundation of China(21965005)the Natural Science Foundation of Guangxi Province(2021GXNSFAA076001)+1 种基金the Project of HighLevel Talents of Guangxi(F-KA18015)Guangxi Technology Base and Talent Subject(GUIKE AD18126001,GUIKE AD20297039)。
文摘The construction of oxide/metal composite catalysts is a competent means of exploiting the electronic interactions between oxide/metal to enhance catalytic activity.In this work,we construct a novel heterogeneous composite(Ru/HfO_(2)-NC)with Ru/HfO2nanoparticles nested in nitrogen-doped porous carbon via a zeolitic imidazole frameworks-assisted(ZIF)co-precipitation and calcination approach.In particular,ZIF guides an in-situ construction of nested configuration and confines the scattered nanoparticles.Strikingly,Ru/HfO_(2)-NC exhibits unusual ORR activity,superb durability,and methanol tolerance in0.1 M KOH solution with high half-wave potential(E1/2)of 0.83 V and follows a near-4e-reaction pathway.Additionally,the ZAB assembled with cathodic Ru/HfO_(2)-NC outputs a power density of 157.3 m W cm^(-2),a specific capacity of 775 mA h g-1Zn,and a prolonged lifespan of 258 h at 5 mA cm^(-2).Meanwhile,the catalyst has demonstrated potential applicability in flexible ZAB.As suggested by experimental results and density functional theory(DFT)analysis,the remarkable property possibly originated from the optimization of the adsorption and desorption of reactive intermediates caused by the reconfiguration of the electronic structure between Ru and HfO_(2).
基金The authors acknowledge the financial support received from 111 Project(B18035)the Fundamental Research Funds for the Central Universities.
文摘Immunotherapy of tumor attracts great attention in the past several years attributing to the potential of completely erasing primary tumor and metastasis.Therefore,pharmaceutical companies developed many antibodies that act as immune check point blockade(ICB),such as Nivolumab,Atezolizumab and Ipilimumab.
基金Supported by the Fundamental Research Funds for the Central Universities,China(Grant No.ZYGX2019Z008)the National Natural Science Foundation of China(Grant No.52072061)。
文摘FeSO_(4) has the characteristics of low cost and theoretical high energy density(799 W·h·kg^(-1) with a two-electron reaction),which can meet the demand for next-generation lithium-ion batteries.Herein,FeSO_(4) as a novel highperformance conversion-reaction type cathode is investigated.We use dopamine as a carbon coating source to increase its electronic conductivity.FeSO_(4)@C demonstrates a high reversible specific capacity(512 mA·h·g^(-1))and a superior cycling performance(482 mA·h·g^(-1) after 250 cycles).In addition,we further study its reaction mechanism.The FeSO_(4) is converted to Fe and Li2SO_(4) during lithium ion insertion and the Fe-Li_(2)SO_(4) grain boundaries further store additional lithium ions.Our findings are valuable in exploring other new conversion-type lithium ion battery cathodes.
基金supported by the Postdoctoral Fellowship Program of CPSF(No.GZC20230333,China).
文摘Nanomedicines have revolutionized disease prevention,diagnosis,and treatment.Since the approval of Liposomal doxorubicin(Doxil)in 1995,various nanomedicines have been successfully developed1.Specifically,the COVID-19 pandemic highlighted the significance of nanomedicines,as lipid nanoparticles facilitated the mRNA vaccines success,thereby remarkable accelerating the development of RNA-drugs2,3.
基金supported by the Natural Science Foundation of Zhejiang Province of China(No.LY22H060003)The National Natural Science Foundation of China(82470903 to LJ)the Natural Science Foundation of Zhejiang Province(LY24C110001 to LJ).
文摘Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity,which are uniquely driven by single-atom constructs.A dramatic increase in antioxidant capacity,158 times more than natural trolox,is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au_(24)Cu_(1).Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis(OA),pH-dependent dendritic mesoporous silica nanoparticles(DMSNs)coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions,thereby enhancing the duration of effectiveness.Nonetheless,achieving high therapeutic efficacy remains a significant challenge.Herein,we describe the construction of a Clusterzymes-DMSNs-PEG complex(CDP)which remarkably diminishes reactive oxygen species(ROS)and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway.In the rabbit ACLT(anterior cruciate ligament transection)model,the CDP complex demonstrated inhibition of matrix metalloproteinase activity,preservation of type Ⅱ collagen and aggregation protein secretion,thus prolonging the clusterzymes’protective influence on joint cartilage structure.Our research underscores the efficacy of the CDP complex in ROS-scavenging,enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment,leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway.This study illuminates the design,composition,and use of DMSNs and clusterzymes in biomedicine,thus charting a promising course for the development of novel therapeutic strategies in alleviating OA.
基金supported by National Natural Science Foundation of China(No.81872806 and 31571016)
文摘Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency,nanoparticles need to change size so as to fully utilize the enhanced permeability and retention(EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin(BSA) protected gold nanocluster(Au NC@CBSA,21.06 nm) to both load indocyanine green(ICG) and act as imaging probe to realize theranostic. Then Au NC@CBSA-ICG was fabricated with negatively charged hyaluronic acid(HA) to form Au NC@CBSAICG@HA, which was about 200 nm to easily retain at tumor site and could be degraded by tumor-specific hyaluronidase into small nanoparticles for deep tumor penetration. The HA shell also endowed Au NC@CBSA-ICG@HA with actively targeting ability and hyaluronidase-dependent drug release. Furthermore, the quenching and recovery of fluorescence revealed the interaction between ICG and carrier, which was essential for the investigation of pharmacokinetic profiles. No matter in vitro or in vivo, Au NC@CBSAICG@HA showed markedly anti-tumor effect, and could suppress 95.0% of tumor growth on mice breast cancer model. All results demonstrated Au NC@CBSA-ICG@HA was potential for breast cancer therapy.
基金supported by National Natural Science Foundation of China(81961138009)111 Project(B18035,China)
文摘As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.
基金supported by National Natural Science Foundation of China (82173762)111 Project (B18035,China)+1 种基金the Key Research and Development Program of Science and Technology Department of Sichuan Province (2022JDJQ0050,2022YFS0334)the Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China。
文摘Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention,which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6(Ce6), hydrophilic chemotherapeutic drug berberrubine(BBR) and matrix metalloproteinase-2(MMP-2) response peptide(PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6(BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine(PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively,we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.
基金supported by National Natural Science Foundation of China(81603057)Research Funds of Sichuan Science and Technology Department(2019YJ0048 and 19YYJC2250,China)the Fundamental Research Funds for the Central Universities(China),and 111 Project(B18035,China)
文摘In order to better evaluate the transport effect of nanoparticles through the nasal mucosa,an in vitro nasal cavity-mimic model was designed based on M cells.The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model.The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability.The differentiation of M cells was observed by upregulated expression of Sialyl Lewis A antigen(SLAA)and integrinβ1,and down-regulated activity of alkaline phosphatase.After targeting M cells with iRGD peptide(cRGDKGPDC),the transport of nanoparticles increased.In vivo,the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration.In the evaluation of immune effect in vivo,the nasal administration of OVA-PLGA/iRGD led to more release of IgG,IFN-γ,IL-2 and secretory IgA(sIgA)compared with OVA@PLGA group.Collectively,the study constructed in vitro M cell model,and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.
基金the National Natural Science Foundation of China(82173762,China)111 Project(B18035,China)+2 种基金the Fundamental of Research Funds for the Central Universities(China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(2022JDJQ0050,China)Project of Chengdu Science and Technology Bureau(2020-GH03-00003-HZ)。
文摘Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy.Herein,a kind of tumor cascade-targeted responsive liposome(NLG919@Lip-pep1)is developed by conjugating polypeptide inhibitor of PD-1 signal pathway(AUNP-12),which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2(MMP-2)cleavable peptide(GPLGVRGD).This targeted liposome is prepared through a mature preparation process,and indoleamine-2,3-dioxygenase(IDO)inhibitor NLG919 was encapsulated into it.Moreover,mediated by the enhanced permeability and retention effect(EPR effect)and AUNP-12,NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues.At the same time,the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12,thus realizing the precise block of PD-1 signal pathway,and restoring the activity of T cells.The exposure of secondary targeting moduleⅡVRGDC-NLG919@Lip mediated tumor cells targeting,and further relieved the immunosuppressive microenvironment.Overall,this study offers a potentially appealing paradigm of a high efficiency,low toxicity,and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer,which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.
基金supported by National Natural Science Foundation of China(No.81961138009)the Fundamental Research Funds for the Central Universities(Nos.SCU2017A001,2018SCUH0024,China)+1 种基金111 Project(No.B18035,China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2020YFS0570,China)
文摘Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in chemotherapy.Catalase(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.
基金supported by the National Natural Science Foundation of China(No.52072061)the Fundamental Research Funds for the Central Universities,China(No.ZYGX2019Z008)the China Postdoctoral Science Foundation Funded Project(No.2019M661941).
文摘Lithium(Li)metal is an ideal anode for the next generation high-energy-density batteries.However,it suffers from dendrite growth,side reactions,and infinite relative volume change.Effective strategies are using porous carbons or surface modification carbons to guide Li deposition into their pores.While the Li deposition behavior is still ambiguous.Here,we systematically determine their deposition behavior in various surface-modified carbons and in different electrolytes via optical microscopy and scanning electron microscopy study.It is found that Li will not spontaneously deposit into the carbon pores,which is significantly dependent on the carbon surface,current density,areal capacity,and electrolyte.Thus,a“lithiophilic”modified commercial hard carbon with Ag is developed as a stable“host”and efficient surface protection derived from the localized high-concentration electrolyte exhibits a pretty low volume change(5.3%)during cycling at a current density of 2 mA·cm^(−2)and an areal capacity of 2 mAh·cm^(−2).This strategy addresses the volume change and dendrite problems by rationally designed host and electrolyte,providing a broad perspective for realizing Li-metal anode.
基金National Natural Science Foundation of China(81961138009)111 Project(B18035)the Key Research and Development Program of Science and Technology Department of Sichuan Province(2020YFS0570).
文摘Although drug delivery systems(DDS)are efficient in brain delivery,they face failure in clinical settings due to their potential toxicity to the central nervous system.Little is known about where the DDS will go after brain delivery,and no specific elimination route that shares a passage with DDS has been verified.Hence,identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation.In this study,we investigated nonreactive gold nanoclusters,which can deliver into the brain,to determine the elimination route of DDS.Subsequently,nanoclusters in the brain were systemically tracked and were found to be critically drained by the glymphatic system from the blood vessel basement membrane to periphery circulations(77.8±23.2%and 43.7±23.4%contribution).Furthermore,the nanoclusters could be actively transported across the blood-brain barrier(BBB)by exosomes(30.5±27.3%and 29.2±7.1%contribution).In addition,microglia promoted glymphatic drainage and passage across the BBB.The simultaneous work of the glymphatic system,BBB,and microglia revealed the fate of gold nanoclusters for brain delivery and provided a basis for further braindelivery DDS.
基金supported by the National Key Research Program of China(grant no.2019YFE0191000)the 13th Five-year Informatization Plan of the Chinese Academy of Sciences(grant nos.XXH13506,XXH13505)the National Science Foundation for Young Scientists of China(grant no.31701157).
文摘Impact Statement We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework(RDF)and implement a server to publish linked open data(LOD).As one of the largest and most comprehensive semantic databases about coronaviruses,the resulted gcCov database demonstrates the capability of using data in the LOD framework to promote correlations between genotypes and phenotypes.These correlations will be helpful for future research on fundamental viral mechanisms and drug and vaccine designs.
