Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria uti...Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation.We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy.Deoxyribonuclease(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal.Also,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as dispersants.On their own,dispersants do not inhibit bacterial growth or kill bacterial pathogens.Both natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like p H-responsive micelles,liposomes or hydrogels.Depending on their composition,nanoparticles can also possess intrinsic dispersant properties.Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells.However,this sudden increase in bacterial concentration can also cause sepsis.Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat.Importantly,biofilm remaining after dispersant administration appears more susceptible to existing antibiotics.Being part of the natural biofilm life-cycle,no signs of"dispersant-resistance"have been observed.Dispersants are therewith promising for the control of infectious biofilms.展开更多
The physiological changes and the mechanism of stress tolerance in tomato were studied under low temperature and low light conditions. Two growth chamber experiments evaluated three temperatures regimes under standard...The physiological changes and the mechanism of stress tolerance in tomato were studied under low temperature and low light conditions. Two growth chamber experiments evaluated three temperatures regimes under standard and relatively low illumination levels with three tomato genotypes. Both experiments used a completely randomized split-plot design (CRD), with temperature regime as the main plot and tomato genotype as the split-plot. The three tomato varieties were “Fenyan No.1”, “SV0313TG”, and “Ousa”. In both experiments, activity of superoxide dismutase (SOD) and peroxidases (POD) in tomato seedlings decreased under low temperature regime and the combination of low temperature and low light. Decreasing temperature had the greatest effect on the increase in enzyme activity. Decrease in POD activity was the greatest under low light and low temperature. The concentration of malondialdehyde (MDA) in plant tissue also decreased under low temperature (20°C/10°C day/night) compared to the standard temperature control (25°C/16°C day/night), but increased at 15°C/5°C day/night temperatures in both experiments and was the greatest under the lowest light and temperature conditions. In both experiments, proline concentrations were the greatest under the standard light intensity (30,000 lux), and proline concentrations increased as temperature decreased. The content of soluble sugar decreased under only low temperature stress but increased under double stresses. The relative value of osmotic potential increased a little under low temperature stress but decreased under double stresses.展开更多
Soilless cultivation has been widely used in tomato(Solanum lycopersicum)production.The objectives of this research are to evaluate the impacts of five nutrient solutions under soilless cultivation on plant growth,fru...Soilless cultivation has been widely used in tomato(Solanum lycopersicum)production.The objectives of this research are to evaluate the impacts of five nutrient solutions under soilless cultivation on plant growth,fruit yield and fruit quality in tomatoes.Four experiments were conducted with six treatments(five nutrient solutions plus one control)in six-cherry tomato cultivars and two big fruited tomato cultivars and 12 traits were observed and evaluated.The results showed that each of the five solutions increased plant growth and fruit yield,and improved the fruit quality.Compared to the control,the nutrient solution treatments increased 91.3%for number of fruits on base fruit cluster,12.1%for height,and 26.3%for stem diameter in the 2017-experiment;17.1%for vitamin C,13.8%for soluble solids,and 20.8%for total soluble sugar content in 2018-experiment one;28.1%for number of fruit cluster,25.8%for fruit yield,9.4%for number of fruit per cluster,and 13.3%for single fruit weight in 2018-experiment two;and 27.7%for vitamin C,14.0%for soluble solids,18.1%for total soluble sugar content,and 14.6%for fruit yield in the 2019-experiment.The solution decreased the chemical nitrate content 16.2%in the 2018-experiment and 43.7%in the 2019-experiment,and decreased the fruit cracking rate by 87%.Treatment 2 with higher nutrient component content showed the best results of the five treatments.The significant high positive correlation among the beneficial traits,fruit yield,soluble solids,total soluble sugar content,and vitamin C,and high negative correlation between each of the four traits and nitrate content were observed,indicating that soilless cultivation can increase tomato yield with higher nutritional components and decreased nitrate content.This research provides useful information for utilizing nutrient solutions supplied to tomato soilless cultivation.展开更多
The success of immunotherapy in pancreatic ductal adenocarcinoma(PDAC)is greatly limited by the scarcity of cytotoxic T lymphocytes(CTLs)in tumor microenvironment,which is mainly due to the physical barrier formed by ...The success of immunotherapy in pancreatic ductal adenocarcinoma(PDAC)is greatly limited by the scarcity of cytotoxic T lymphocytes(CTLs)in tumor microenvironment,which is mainly due to the physical barrier formed by a dense extracellular matrix(ECM).Here we reported a potent strategy to rectify the CTLs infiltration in PDAC by synergistically deactivating cancer-associated fibroblasts(CAFs)and driving T-Cell migration into tumor microenvironment.This combination therapy is achieved by co-delivery of vitamin D receptor ligand(calcipo-triol,Cal)and chemokine(CXCL9)using nanochaperone(nChap)delivery platform.We demonstrate that Cal reverses the activated CAFs to quiescence for resulting in a loosened ECM,while the CXCL9 gradient increases the recruitment signal of CD8+T cells,synergistically enhancing the intratumoral infiltration of CD8+T cells.Noteworthily,this system(Cal@nChap-CXCL9)promotes both the penetration of immunotherapeutic(anti-PD-1)and chemotherapeutic(gemcitabine),significantly enhancing the efficacy of chemo-immunotherapy for advanced large Panc02 tumors.This study provides a promising strategy for enhanced PDAC immunotherapy.展开更多
Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, ...Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.展开更多
For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insuli...For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid(PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.展开更多
Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of e...Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.展开更多
In recent years,intracellular delivery of protein drugs has attracted great attention,and polymer-based systems have been extensively exploited to develop efficient and safe carriers.However,efficient intracellular de...In recent years,intracellular delivery of protein drugs has attracted great attention,and polymer-based systems have been extensively exploited to develop efficient and safe carriers.However,efficient intracellular delivery of protein drugs remains a challenge because of the cell membrane barrier and endosome entrapment.Herein,we report a protein@PP-Zn nanocomplex,which consists of an imidazole-containing block polymer poly(ethylene glycol)-block-poly(β-amino ester)(PEG-b-PAE(Im),PP),zinc ions,and protein drugs,for efficient intracellular protein delivery.PEG-b-PAE(Im)could conjugate proteins via the bridging effect of zinc ions which simultaneously coordinate with imidazole groups on polymer and electron donor groups,such as imidazole and primary amine groups,on protein to improve the loading stability of proteins.Under a slightly acidic environment near cancer cells,the protonation of PAE(Im)backbone increases the positive charge density of the nanocomplex and promotes endocytosis.While under a more acidic environment in endosomes,further protonation of imidazole groups leads to the disintegration of the nanocomplex and the breakdown of endosomes because of the proton sponge effect.Finally,protein is released into the cytoplasm.With the assistance of the nanocomplex,proteins with different sizes and isoelectric points are effectively delivered into cells.This work provides a stable,efficient and universal strategy for intracellular protein delivery.展开更多
Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential ...Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application.In this work,a calixarene-integrated nanoDDS(CanD)that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented.The hypoxia-responsive calixarene(SAC4A)exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B(RhB)under normoxic condition while decreasing the binding affinity under hypoxic condition,which leads to the drug release and fluorescence recovery simultaneously.Furthermore,the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability,resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice.Moreover,CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-vip interaction with SAC4A.展开更多
Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon coating.However,the properties of a suppo...Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon coating.However,the properties of a support-surface responsible for maintaining correct sidedness and fluidity are unknown.Here,we briefly review the properties of natural membranes and membrane-isolation methods,with focus on the asymmetric distribution of functional groups in natural membranes(sidedness)and the ability of molecules to float across a membrane to form functional domains(fluidity).This review concludes that hydrophilic sugar-residues of glycoproteins in the outer-leaflet of cell membranes direct the more hydrophobic inner-leaflet towards a support-surface to create a correctly-sided membrane coating,regardless of electrostatic double-layer interactions.On positively-charged support-surfaces however,strong,electrostatic double-layer attraction of negatively-charged membranes can impede homogeneous coating.In correctly-sided membrane coatings,fluidity is maintained regardless of whether the surface carries a positive or negative charge.However,membranes are frozen on positively-charged,highly-curved,small nanoparticles and localized nanoscopic structures on a support-surface.This leaves an unsupported membrane coating in between nanostructures on planar support-surfaces that is in dual-sided contact with its aqueous environment,yielding enhanced fluidity in membrane coatings on nanostructured,planar support-surfaces as compared with smooth ones.展开更多
New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms.This work reports the facile synthesis of antimicrobial dynamic covalent...New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms.This work reports the facile synthesis of antimicrobial dynamic covalent nano-networks(aDCNs)composing antibiotics bearing multiple primary amines,polyphenols,and a cross-linker acylphenylboronic acid.Mechanistically,the iminoboronate bond drives the formation of aDCNs,facilitates their stability,and renders them highly responsive to stimuli,such as low pH and high H2O2 levels.Besides,the representative A1B1C1 networks,composed of polymyxin B1(A1),2-formylphenylboronic acid(B1),and quercetin(C1),inhibit biofilm formation of drug-resistant Escherichia coli,eliminate the mature biofilms,alleviate macrophage inflammation,and minimize the side effects of free polymyxins.Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 networks are also observed in a peritoneal infection model.The facile synthesis,excellent antimicrobial performance,and biocompatibility of these aDCNs potentiate them as a much-needed alternative in current antimicrobial pipelines.展开更多
The deposition of highly ordered amyloid fibrils is recognized as a hallmark of amyloidosis diseases such as Alzheimer’s disease and Parkinson’s disease.Disaggregating the amyloid fibrils is considered as one of the...The deposition of highly ordered amyloid fibrils is recognized as a hallmark of amyloidosis diseases such as Alzheimer’s disease and Parkinson’s disease.Disaggregating the amyloid fibrils is considered as one of the effective strategies for the control and treatment of amyloidosis diseases.In this article,by simulating the function of natural molecular chaperones,co-assembled block copolymer micelles with coordination groups of nitrilotriacetic acid(NTA)and hydrophobic microdomains of poly(Nisopropylacrylamide)(PNIPAM)on the surface were used as nanochaperones(n Chaps)to disaggregate amyloid insulin fibrils.Zinc ions chelated by NTA can bind the histidine imidazole residues while the PNIPAM microdomains can interact with the exposed hydrophobic sites on the amyloid insulin fibrils,which synergistically perturb the stability of amyloid insulin fibrils,loosen their structure,and finally promote their disaggregation.A combination of characterizations with fluorescence spectroscopy,transmission electron microscopy(TEM),dynamic hight scattering(DLS),and quartz crystal microbalance(QCM)demonstrated that mature amyloid insulin fibrils were completely disaggregated after incubating with n Chaps for 90 h.This study may provide a promising strategy for the development of n Chaps for the treatment of amyloidosis diseases.展开更多
This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA comple...This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA complex exhibited a 12-fold enhancement of the molar extinction coefficient in the nearinfrared(NIR)region relative to aqueous cupric acetate.Inspired by this interesting finding,we formulated these photothermal materials into colloidally dispersed nanoparticles via a technique that combined nanoprecipitation and in situ surface polymerization for antibacterial studies.The resultant nanoparticles exhibited rapid and stable photothermal responses to NIR irradiation,with a 4-fold enhanced photothermal conversion efficiency relative to aqueous cupric acetate.Since a positively charged monomer was incorporated during in situ surface polymerization,these positively charged nanoparticles were ingested efficiently and subsequently digested by drug-resistant bacteria.By combining the LA-mediated membrane-damaging effect,copper-mediated Fenton-like reaction,as well as the photothermal effect of the copper–LA complex,a broad-spectrum,multimodal,and synergistic antibacterial effect was achieved both in vitro and in vivo,with the killing efficiency up to 99.99%for ampicillin-resistant Escherichia coli(Ampr E.coli)and 99.9999%for methicillinresistant Staphylococcus aureus(MRSA).Our newly developed nanobiocide represents a class of exceptional broad-spectrum antibacterial materials,holding great potential for treating drug-resistant infections in clinical settings.展开更多
A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly（ethylene glycol）-blo...A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly（ethylene glycol）-block- poly（4-vinylpyridine-co-N-heptyl-4-vinylpyridine） （PEG-b-P（4VP-co-4VPHep））, tetrakis（4-sulfonatophenyl）porphinato iron（II） （Fe（II）TPPS） and β-cyclodextrin （β-CD）. The μ-oxo dimer of Fe（II）TPPS was successfully inhibited because the Fe（II）TPPS was included into the cavities of β-CDs through host-vip interaction. Fe（II）TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-vip inclusion （β-CD/Fe（II）TPPS） was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe（II）TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O4^2- ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts （Fe（II）TPPS（O2）） were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.展开更多
Herein,three novel tetraphenylethylene hydrazone chemosensors TC12,SC16,and TC16 are prepared for the selective detection of F−.Two NH and one C=N units are incorporated into the sensors for better colorimetric respon...Herein,three novel tetraphenylethylene hydrazone chemosensors TC12,SC16,and TC16 are prepared for the selective detection of F−.Two NH and one C=N units are incorporated into the sensors for better colorimetric responses,whereas the tetraphenyl unit is in charge of the aggregation-induced emission effect.Among them,compounds SC16 and TC16 form stable gels with some organic solvents.All the tetrahydrofuran/H2O solutions of the three compounds exhibit aggregation-induced emission effect,whereby the fluorescence emission increases by varying degrees with the volume of poor solvent water.Moreover,good aggregation-induced emission effects are observed in the self-assembly of SC16 and TC16.As a sample chemosensor,TC12 in tetrahydrofuran responds to F−selectively with high sensitivity,with the colorimetric and fluorometric detection limits of 8.25×10^(−7) mol·L^(-1) and 2.69×10^(−7) mol·L^(-1),respectively.The reversible gel-sol-gel phase transition and color changes indicate that both SC16-dimethyl sulfoxide and TC16-ethyl acetate gels specifically respond to F-with good sensitivity.The detection results are well supported by ultraviolet-visible spectroscopy,fluorescent spectroscopy,and 1H nuclear magnetic resonance.More importantly,the driving forces of gelation are visually clarified through the single crystal X-ray analysis of compound TOMe.展开更多
Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding.However,synthesis of such molecules is a big challenge.The concept of“aggregate science”provid...Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding.However,synthesis of such molecules is a big challenge.The concept of“aggregate science”provides insights to construct chemical entities(aggregates)beyond molecular levels to mimic both the structure and function of natural chaperone.Inspired by this concept,herein we fabricate a novel multi-interaction(i.e.,electrostatic and hydrophobic interaction)cooperative nanochaperone(multi-co-nChap)to regulating protein folding.This multi-co-nChap is fabricated by rationally introducing electrostatic interactions to the surface(corona)and confined hydrophobic microdomains(shell)of traditional single-hydrophobic interaction nanochaperone.We demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains,while the shell electrostatic interaction balances the capture and release of clients.By finely synergizing corona electrostatic attraction with shell electrostatic repulsion and hydrophobic interaction,the optimized multi-co-nChap effectively facilitated de novo folding of nascent polypeptides.Moreover,the synergy between corona electrostatic attraction,shell electrostatic attraction and shell hydrophobic interaction significantly enhanced the capability of multi-co-nChap to protect native proteins from denaturation at harsh temperatures.This work provides important insights for understanding and design of nanochaperone,which is a kind of ordered aggregate with chaperone-like activity that beyond the level of single molecule.展开更多
Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection sit...Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.展开更多
The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge....The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge.Herein,a self-regulated pho-totheranostic nanosystem with single wavelength-triggered photothermal therapy(PTT)/photodynamic therapy(PDT)transformation and oxygen supply for multi-modal synergistic therapy of bacterial biofilm infections is presented.This approach combines a eutectic mixture of natural phase-change materials(PCMs)and an aggregation-induced emission(AIE)phototheranostic agent TPA-ICN to form col-loidally stable nanopartcicles(i.e.AIE@PCM NPs).The reversible solid-liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN,enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs.Addition-ally,oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT.The nanosystem exhibits outstanding therapeu-tic efficacy against bacterial biofilms both in vitro and in vivo,with an antibacterial efficiency of 99.99%.This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release,holding great promise in the safe and efficient treatment of bacterial biofilm infections.展开更多
Controlling the growth of bacterial biofilms in a specific pattern greatly enhances the study of cell-to-cell interactions and paves the way for expanding their biolog-ical applications.However,the development of simp...Controlling the growth of bacterial biofilms in a specific pattern greatly enhances the study of cell-to-cell interactions and paves the way for expanding their biolog-ical applications.However,the development of simple,cost-effective,and highly resolved biopatterning approaches remains a persistent challenge.Herein,a pio-neering photodynamic biopatterning technique for the creation of living bacterial biofilms with customized geometries at high resolutions is presented.First of all,an outstanding aggregation-induced emission photosensitizer is synthesized to enable efficient photodynamic bacterial killing at a low concentration.By combining with custom-designed photomasks featuring both opaque and transparent patterns,the viability of photosensitizer-coated bacteria is successfully manipulated by control-ling the degree of light transmittance.This process leads to the formation of living bacterial biofilms with specific patterns replicated from the photomask.Such an innovative strategy can be employed to generate living bacterial biofilms composed of either mono-or multispecies,with a spatial resolution of approximately 24µm.Furthermore,its potential applications in information storage/encryption and antibi-otic screening are explored.This study provides an alternative way to understand and investigate the intricate interactions among bacteria within 3D biofilms,hold-ing great promise in the controlled fabrication of dynamic biological systems for advanced applications.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.21620102005 and 51933006)。
文摘Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation.We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy.Deoxyribonuclease(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal.Also,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as dispersants.On their own,dispersants do not inhibit bacterial growth or kill bacterial pathogens.Both natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like p H-responsive micelles,liposomes or hydrogels.Depending on their composition,nanoparticles can also possess intrinsic dispersant properties.Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells.However,this sudden increase in bacterial concentration can also cause sepsis.Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat.Importantly,biofilm remaining after dispersant administration appears more susceptible to existing antibiotics.Being part of the natural biofilm life-cycle,no signs of"dispersant-resistance"have been observed.Dispersants are therewith promising for the control of infectious biofilms.
文摘The physiological changes and the mechanism of stress tolerance in tomato were studied under low temperature and low light conditions. Two growth chamber experiments evaluated three temperatures regimes under standard and relatively low illumination levels with three tomato genotypes. Both experiments used a completely randomized split-plot design (CRD), with temperature regime as the main plot and tomato genotype as the split-plot. The three tomato varieties were “Fenyan No.1”, “SV0313TG”, and “Ousa”. In both experiments, activity of superoxide dismutase (SOD) and peroxidases (POD) in tomato seedlings decreased under low temperature regime and the combination of low temperature and low light. Decreasing temperature had the greatest effect on the increase in enzyme activity. Decrease in POD activity was the greatest under low light and low temperature. The concentration of malondialdehyde (MDA) in plant tissue also decreased under low temperature (20°C/10°C day/night) compared to the standard temperature control (25°C/16°C day/night), but increased at 15°C/5°C day/night temperatures in both experiments and was the greatest under the lowest light and temperature conditions. In both experiments, proline concentrations were the greatest under the standard light intensity (30,000 lux), and proline concentrations increased as temperature decreased. The content of soluble sugar decreased under only low temperature stress but increased under double stresses. The relative value of osmotic potential increased a little under low temperature stress but decreased under double stresses.
文摘Soilless cultivation has been widely used in tomato(Solanum lycopersicum)production.The objectives of this research are to evaluate the impacts of five nutrient solutions under soilless cultivation on plant growth,fruit yield and fruit quality in tomatoes.Four experiments were conducted with six treatments(five nutrient solutions plus one control)in six-cherry tomato cultivars and two big fruited tomato cultivars and 12 traits were observed and evaluated.The results showed that each of the five solutions increased plant growth and fruit yield,and improved the fruit quality.Compared to the control,the nutrient solution treatments increased 91.3%for number of fruits on base fruit cluster,12.1%for height,and 26.3%for stem diameter in the 2017-experiment;17.1%for vitamin C,13.8%for soluble solids,and 20.8%for total soluble sugar content in 2018-experiment one;28.1%for number of fruit cluster,25.8%for fruit yield,9.4%for number of fruit per cluster,and 13.3%for single fruit weight in 2018-experiment two;and 27.7%for vitamin C,14.0%for soluble solids,18.1%for total soluble sugar content,and 14.6%for fruit yield in the 2019-experiment.The solution decreased the chemical nitrate content 16.2%in the 2018-experiment and 43.7%in the 2019-experiment,and decreased the fruit cracking rate by 87%.Treatment 2 with higher nutrient component content showed the best results of the five treatments.The significant high positive correlation among the beneficial traits,fruit yield,soluble solids,total soluble sugar content,and vitamin C,and high negative correlation between each of the four traits and nitrate content were observed,indicating that soilless cultivation can increase tomato yield with higher nutritional components and decreased nitrate content.This research provides useful information for utilizing nutrient solutions supplied to tomato soilless cultivation.
基金supported by National Natural Science Foundation of China(Grant Number:52373153,51933006,52293383)National Key Research and Development Program of China(Project number:2022YFA1205702)+1 种基金the Natural Science Foundation of Tianjin,China(Grant Number:24JCYBJC01830)Haihe Laboratory of Sus-tainable Chemical Transformations(Project number:YYJC202102).
文摘The success of immunotherapy in pancreatic ductal adenocarcinoma(PDAC)is greatly limited by the scarcity of cytotoxic T lymphocytes(CTLs)in tumor microenvironment,which is mainly due to the physical barrier formed by a dense extracellular matrix(ECM).Here we reported a potent strategy to rectify the CTLs infiltration in PDAC by synergistically deactivating cancer-associated fibroblasts(CAFs)and driving T-Cell migration into tumor microenvironment.This combination therapy is achieved by co-delivery of vitamin D receptor ligand(calcipo-triol,Cal)and chemokine(CXCL9)using nanochaperone(nChap)delivery platform.We demonstrate that Cal reverses the activated CAFs to quiescence for resulting in a loosened ECM,while the CXCL9 gradient increases the recruitment signal of CD8+T cells,synergistically enhancing the intratumoral infiltration of CD8+T cells.Noteworthily,this system(Cal@nChap-CXCL9)promotes both the penetration of immunotherapeutic(anti-PD-1)and chemotherapeutic(gemcitabine),significantly enhancing the efficacy of chemo-immunotherapy for advanced large Panc02 tumors.This study provides a promising strategy for enhanced PDAC immunotherapy.
基金supported by the National Natural Science Foundation of China (52073218, 22135005, 51873162, 51933006,51988102, 52122310, 22075050, 51833008, 51733006, 51733001,52122304)Jiangsu Province Science Foundation for Youths(BK20200241)+3 种基金Science and Technology Commission of Shanghai Municipality (20JC1414902, 21511104900)Shanghai Municipal Education Commission (2017-01-07-00-07-E00062)the National Key Research and Development Program (2021YFA1201200) of Chinathe Zhejiang Provincial Key Research and Development Program (2020C01123)。
文摘Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.
基金supported by the National Natural Science Foundation of China(51603105,51773099,51390483,91527306,21620102005)the Program for Changjiang Scholars and Innovative Research Team in University(IRT1257)
文摘For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid(PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.
基金This work is supported by the National Natural Science Foundation of China （NSFC, Nos. 91127045, 51390483, 51473319, 51303025, 81401439 and 51343007）, YG2012MS38 and China Postdoctoral Science Foundation （No. 2014M551399）.
文摘Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.
基金supported by the National Natural Science Foundation of China(51773099,52203184,22275043,51933006)。
文摘In recent years,intracellular delivery of protein drugs has attracted great attention,and polymer-based systems have been extensively exploited to develop efficient and safe carriers.However,efficient intracellular delivery of protein drugs remains a challenge because of the cell membrane barrier and endosome entrapment.Herein,we report a protein@PP-Zn nanocomplex,which consists of an imidazole-containing block polymer poly(ethylene glycol)-block-poly(β-amino ester)(PEG-b-PAE(Im),PP),zinc ions,and protein drugs,for efficient intracellular protein delivery.PEG-b-PAE(Im)could conjugate proteins via the bridging effect of zinc ions which simultaneously coordinate with imidazole groups on polymer and electron donor groups,such as imidazole and primary amine groups,on protein to improve the loading stability of proteins.Under a slightly acidic environment near cancer cells,the protonation of PAE(Im)backbone increases the positive charge density of the nanocomplex and promotes endocytosis.While under a more acidic environment in endosomes,further protonation of imidazole groups leads to the disintegration of the nanocomplex and the breakdown of endosomes because of the proton sponge effect.Finally,protein is released into the cytoplasm.With the assistance of the nanocomplex,proteins with different sizes and isoelectric points are effectively delivered into cells.This work provides a stable,efficient and universal strategy for intracellular protein delivery.
基金National Key Research and Development Programs of China(No.2018YFA0209700)National Natural Science Foundation of China(NSFC,No.22077073)+1 种基金Frontiers Science Center for New Organic Matter(No.63181206)Fundamental Research Funds for the Central Universities(Nankai University,No.63206015).
文摘Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application.In this work,a calixarene-integrated nanoDDS(CanD)that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented.The hypoxia-responsive calixarene(SAC4A)exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B(RhB)under normoxic condition while decreasing the binding affinity under hypoxic condition,which leads to the drug release and fluorescence recovery simultaneously.Furthermore,the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability,resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice.Moreover,CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-vip interaction with SAC4A.
基金financially supported by the National Key Research and Development Program of China(2017YFE0131700)the National Natural Science Foundation of China(52293383)the Soochow University,the Nankai University,and UMCG,Groningen,The Netherlands.
文摘Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon coating.However,the properties of a support-surface responsible for maintaining correct sidedness and fluidity are unknown.Here,we briefly review the properties of natural membranes and membrane-isolation methods,with focus on the asymmetric distribution of functional groups in natural membranes(sidedness)and the ability of molecules to float across a membrane to form functional domains(fluidity).This review concludes that hydrophilic sugar-residues of glycoproteins in the outer-leaflet of cell membranes direct the more hydrophobic inner-leaflet towards a support-surface to create a correctly-sided membrane coating,regardless of electrostatic double-layer interactions.On positively-charged support-surfaces however,strong,electrostatic double-layer attraction of negatively-charged membranes can impede homogeneous coating.In correctly-sided membrane coatings,fluidity is maintained regardless of whether the surface carries a positive or negative charge.However,membranes are frozen on positively-charged,highly-curved,small nanoparticles and localized nanoscopic structures on a support-surface.This leaves an unsupported membrane coating in between nanostructures on planar support-surfaces that is in dual-sided contact with its aqueous environment,yielding enhanced fluidity in membrane coatings on nanostructured,planar support-surfaces as compared with smooth ones.
基金supported by the National Natural Science Foundation of China(Grant Nos.52203184,22275043,51773099,52293380,and 52293383)Startup Fund of Wenzhou Institute,University of Chinese Academy of Sciences(Grant No.WIUCASQD2021022)+1 种基金Key Laboratory of Functional Polymer Materials,Ministry of Education(Grant No.KLFPM202202)Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province(Grant No.2022E10022).
文摘New antimicrobial strategies are urgently needed to meet the challenges posed by the emergence of drug-resistant bacteria and bacterial biofilms.This work reports the facile synthesis of antimicrobial dynamic covalent nano-networks(aDCNs)composing antibiotics bearing multiple primary amines,polyphenols,and a cross-linker acylphenylboronic acid.Mechanistically,the iminoboronate bond drives the formation of aDCNs,facilitates their stability,and renders them highly responsive to stimuli,such as low pH and high H2O2 levels.Besides,the representative A1B1C1 networks,composed of polymyxin B1(A1),2-formylphenylboronic acid(B1),and quercetin(C1),inhibit biofilm formation of drug-resistant Escherichia coli,eliminate the mature biofilms,alleviate macrophage inflammation,and minimize the side effects of free polymyxins.Excellent bacterial eradication and inflammation amelioration efficiency of A1B1C1 networks are also observed in a peritoneal infection model.The facile synthesis,excellent antimicrobial performance,and biocompatibility of these aDCNs potentiate them as a much-needed alternative in current antimicrobial pipelines.
基金supported by the National Natural Science Foundation of China(51773099,51933006)。
文摘The deposition of highly ordered amyloid fibrils is recognized as a hallmark of amyloidosis diseases such as Alzheimer’s disease and Parkinson’s disease.Disaggregating the amyloid fibrils is considered as one of the effective strategies for the control and treatment of amyloidosis diseases.In this article,by simulating the function of natural molecular chaperones,co-assembled block copolymer micelles with coordination groups of nitrilotriacetic acid(NTA)and hydrophobic microdomains of poly(Nisopropylacrylamide)(PNIPAM)on the surface were used as nanochaperones(n Chaps)to disaggregate amyloid insulin fibrils.Zinc ions chelated by NTA can bind the histidine imidazole residues while the PNIPAM microdomains can interact with the exposed hydrophobic sites on the amyloid insulin fibrils,which synergistically perturb the stability of amyloid insulin fibrils,loosen their structure,and finally promote their disaggregation.A combination of characterizations with fluorescence spectroscopy,transmission electron microscopy(TEM),dynamic hight scattering(DLS),and quartz crystal microbalance(QCM)demonstrated that mature amyloid insulin fibrils were completely disaggregated after incubating with n Chaps for 90 h.This study may provide a promising strategy for the development of n Chaps for the treatment of amyloidosis diseases.
基金supported by the start-up funding from Nankai University(to C.Z.)the National Natural Science Foundation of China(nos.52003123,21620102005,and 81722026)the CAMS Innovation Fund for Medical Sciences(no.2016-I2M-3-022).
文摘This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA complex exhibited a 12-fold enhancement of the molar extinction coefficient in the nearinfrared(NIR)region relative to aqueous cupric acetate.Inspired by this interesting finding,we formulated these photothermal materials into colloidally dispersed nanoparticles via a technique that combined nanoprecipitation and in situ surface polymerization for antibacterial studies.The resultant nanoparticles exhibited rapid and stable photothermal responses to NIR irradiation,with a 4-fold enhanced photothermal conversion efficiency relative to aqueous cupric acetate.Since a positively charged monomer was incorporated during in situ surface polymerization,these positively charged nanoparticles were ingested efficiently and subsequently digested by drug-resistant bacteria.By combining the LA-mediated membrane-damaging effect,copper-mediated Fenton-like reaction,as well as the photothermal effect of the copper–LA complex,a broad-spectrum,multimodal,and synergistic antibacterial effect was achieved both in vitro and in vivo,with the killing efficiency up to 99.99%for ampicillin-resistant Escherichia coli(Ampr E.coli)and 99.9999%for methicillinresistant Staphylococcus aureus(MRSA).Our newly developed nanobiocide represents a class of exceptional broad-spectrum antibacterial materials,holding great potential for treating drug-resistant infections in clinical settings.
文摘A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly（ethylene glycol）-block- poly（4-vinylpyridine-co-N-heptyl-4-vinylpyridine） （PEG-b-P（4VP-co-4VPHep））, tetrakis（4-sulfonatophenyl）porphinato iron（II） （Fe（II）TPPS） and β-cyclodextrin （β-CD）. The μ-oxo dimer of Fe（II）TPPS was successfully inhibited because the Fe（II）TPPS was included into the cavities of β-CDs through host-vip interaction. Fe（II）TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-vip inclusion （β-CD/Fe（II）TPPS） was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe（II）TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O4^2- ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts （Fe（II）TPPS（O2）） were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.
基金financially supported by the National Key Research and Development Program of China(Grant No.2018YFA0903700)。
文摘Herein,three novel tetraphenylethylene hydrazone chemosensors TC12,SC16,and TC16 are prepared for the selective detection of F−.Two NH and one C=N units are incorporated into the sensors for better colorimetric responses,whereas the tetraphenyl unit is in charge of the aggregation-induced emission effect.Among them,compounds SC16 and TC16 form stable gels with some organic solvents.All the tetrahydrofuran/H2O solutions of the three compounds exhibit aggregation-induced emission effect,whereby the fluorescence emission increases by varying degrees with the volume of poor solvent water.Moreover,good aggregation-induced emission effects are observed in the self-assembly of SC16 and TC16.As a sample chemosensor,TC12 in tetrahydrofuran responds to F−selectively with high sensitivity,with the colorimetric and fluorometric detection limits of 8.25×10^(−7) mol·L^(-1) and 2.69×10^(−7) mol·L^(-1),respectively.The reversible gel-sol-gel phase transition and color changes indicate that both SC16-dimethyl sulfoxide and TC16-ethyl acetate gels specifically respond to F-with good sensitivity.The detection results are well supported by ultraviolet-visible spectroscopy,fluorescent spectroscopy,and 1H nuclear magnetic resonance.More importantly,the driving forces of gelation are visually clarified through the single crystal X-ray analysis of compound TOMe.
基金National Natural Science Foundation of China,Grant/Award Numbers:51933006,52373153,52293383National Key Research and Development Program of China,Grant/Award Number:2022YFA1205702Haihe Laboratory of Sustainable Chemical Transformations,Grant/Award Number:YYJC202102。
文摘Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding.However,synthesis of such molecules is a big challenge.The concept of“aggregate science”provides insights to construct chemical entities(aggregates)beyond molecular levels to mimic both the structure and function of natural chaperone.Inspired by this concept,herein we fabricate a novel multi-interaction(i.e.,electrostatic and hydrophobic interaction)cooperative nanochaperone(multi-co-nChap)to regulating protein folding.This multi-co-nChap is fabricated by rationally introducing electrostatic interactions to the surface(corona)and confined hydrophobic microdomains(shell)of traditional single-hydrophobic interaction nanochaperone.We demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains,while the shell electrostatic interaction balances the capture and release of clients.By finely synergizing corona electrostatic attraction with shell electrostatic repulsion and hydrophobic interaction,the optimized multi-co-nChap effectively facilitated de novo folding of nascent polypeptides.Moreover,the synergy between corona electrostatic attraction,shell electrostatic attraction and shell hydrophobic interaction significantly enhanced the capability of multi-co-nChap to protect native proteins from denaturation at harsh temperatures.This work provides important insights for understanding and design of nanochaperone,which is a kind of ordered aggregate with chaperone-like activity that beyond the level of single molecule.
基金financially supported by the National Natural Science Foundation of China(51933006,21620102005)The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT35031).
文摘Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms.However,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are short-lived.Therefore,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of reactive-oxygen-species.Glucose-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) generated.Using an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm.Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative bacteria.Additional efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated in-biofilm.In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital window.Moreover,vancomycin-resistant,abdominal S.aureus biofilms could be eradicated consuming solely endogenous glucose,without any glucose addition.Herewith,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.
基金National Natural Science Foundation of China,Grant/Award Numbers:92163126,52293380,52293383Fundamental Research Funds for the Central Universities,Grant/Award Numbers:63241614,63233051Beijing National Laboratory for Molecular Sciences,Grant/Award Number:BNLMS202308。
文摘The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge.Herein,a self-regulated pho-totheranostic nanosystem with single wavelength-triggered photothermal therapy(PTT)/photodynamic therapy(PDT)transformation and oxygen supply for multi-modal synergistic therapy of bacterial biofilm infections is presented.This approach combines a eutectic mixture of natural phase-change materials(PCMs)and an aggregation-induced emission(AIE)phototheranostic agent TPA-ICN to form col-loidally stable nanopartcicles(i.e.AIE@PCM NPs).The reversible solid-liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN,enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs.Addition-ally,oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT.The nanosystem exhibits outstanding therapeu-tic efficacy against bacterial biofilms both in vitro and in vivo,with an antibacterial efficiency of 99.99%.This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release,holding great promise in the safe and efficient treatment of bacterial biofilm infections.
基金National Natural Science Foundation of China,Grant/Award Numbers:92163126,52293380,52293383Beijing National Laboratory for Molecular Sciences,Grant/Award Number:BNLMS202308Fundamental Research Funds for the Central Universities,Grant/Award Numbers:63223030,63223017。
文摘Controlling the growth of bacterial biofilms in a specific pattern greatly enhances the study of cell-to-cell interactions and paves the way for expanding their biolog-ical applications.However,the development of simple,cost-effective,and highly resolved biopatterning approaches remains a persistent challenge.Herein,a pio-neering photodynamic biopatterning technique for the creation of living bacterial biofilms with customized geometries at high resolutions is presented.First of all,an outstanding aggregation-induced emission photosensitizer is synthesized to enable efficient photodynamic bacterial killing at a low concentration.By combining with custom-designed photomasks featuring both opaque and transparent patterns,the viability of photosensitizer-coated bacteria is successfully manipulated by control-ling the degree of light transmittance.This process leads to the formation of living bacterial biofilms with specific patterns replicated from the photomask.Such an innovative strategy can be employed to generate living bacterial biofilms composed of either mono-or multispecies,with a spatial resolution of approximately 24µm.Furthermore,its potential applications in information storage/encryption and antibi-otic screening are explored.This study provides an alternative way to understand and investigate the intricate interactions among bacteria within 3D biofilms,hold-ing great promise in the controlled fabrication of dynamic biological systems for advanced applications.
