Besides our previous experimental discovery （Zhao Y R, et al. 2015 Langmuir, 31, 12975） that acetonitrile （ACN） can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK （KI4K...Besides our previous experimental discovery （Zhao Y R, et al. 2015 Langmuir, 31, 12975） that acetonitrile （ACN） can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK （KI4K） in aqueous solution, further experiments reported in this work demonstrate that ACN can also tune the mass of the self-assembled nanostructures. To understand the microscopic mechanism how ACN molecules interfere peptide self-assembly process, we conducted a series of molecular dynamics simulations on a monomer, a cross-β sheet structure, and a proto-fibril of KI4K in pure water, pure ACN, and ACN-water mixtures, respectively. The simulation results indicate that ACN enhances the intra-sheet interaction dominated by the hydrogen bonding （H-bonding） interactions between peptide backbones, but weakens the inter-sheet interaction dominated by the interactions between hydrophobic side chains. Through analyzing the correlations between different groups of solvent and peptides and the solvent behaviors around the proto-fibril, we have found that both the polar and nonpolar groups of ACN play significant roles in causing the opposite effects on intermolecular interactions among peptides. The weaker correlation of the polar group of ACN than water molecule with the peptide backbone enhances H-bonding interactions between peptides in the proto-fibril. The stronger correlation of the nonpolar group of ACN than water molecule with the peptide side chain leads to the accumulation of ACN molecules around the proto-fibril with their hydrophilic groups exposed to water, which in turn allows more water molecules close to the proto-fibril surface and weakens the inter-sheet interactions. The two opposite effects caused by ACN form a microscopic mechanism clearly explaining our experimental observations.展开更多
Under appropriate physicochemical conditions, short peptide fragments and their synthetic mimics have been shown to form elongated cross-fl nanostructures through self-assembly. The self-assembly process and the resul...Under appropriate physicochemical conditions, short peptide fragments and their synthetic mimics have been shown to form elongated cross-fl nanostructures through self-assembly. The self-assembly process and the resultant peptide nanos- tructures are not only related to neurodegenerative diseases but also provide inspiration for the development of novel bionanomaterials. Both experimental and theoretical studies on peptide self-assembly have shown that the self-assembly process spans multiple time and length scales and is hierarchical, β-sheet self-assembly consists of three sub-processes from the microscopic to the mesoscopic level： β-sheet locking, lateral stacking, and morphological transformation. De- tailed atomistic simulation studies have provided insight into the early stages of peptide nanostructure formation and the interplay between different non-covalent interactions at the microscopic level. This review gives a brief introduction of the hierarchical peptide self-assembly process and focuses on the roles of various non-covalent interactions in the sub-processes based on recent simulation, experimental, and theoretical studies.展开更多
In order to study the biocompatibility of self-assembled FGL peptide nanofibers scaffold with neural stem cells （NSCs）, FGL pepitide-amphiphile （FGL-PA） was synthesized by solid-phase peptide synthesis technique. ...In order to study the biocompatibility of self-assembled FGL peptide nanofibers scaffold with neural stem cells （NSCs）, FGL pepitide-amphiphile （FGL-PA） was synthesized by solid-phase peptide synthesis technique. The diluted hydrochloric acid was added into FGL-PA solution to reduce the PH value and accordingly induce self-assembly. The morphological features of the assembled material were studied by transmission electron microscope. NSCs were cultured and added with self-assembled FGL-PA. CCK-8 kit was used to test its effect on the proliferation of NSCs. The differentiation of NSCs was also tested after FGL-PA assembled material added. The experimental results showed that FGL-PA could be self-assembled to form a hydrogel. TEM analysis showed the self-assembled hydrogel was nanofibers with diameter of 10-20 nm and length of hundreds nanometers. FGL-PA with concentrations of 50,100, or 200 mg/L could promote the proliferation of NSCs, and absorbance of them was increased （P〈0.05）. The rate of neurons differentiated from NSCs was improved greatly by FGL-PA assembled material compared with control （P〈0.05）. The findings suggested that FGL-PA could self-assemble to nanofiber hydrogel, which had good biocompatibility with NSCs.展开更多
Peptide GAV-9 is derived from 3 different disease related proteins. The self-assembly of GAV-9 in a water nanofilm attracted much attention recently. We studied how the temperature factor influenced the peptide selfas...Peptide GAV-9 is derived from 3 different disease related proteins. The self-assembly of GAV-9 in a water nanofilm attracted much attention recently. We studied how the temperature factor influenced the peptide selfassembly in a water nanofilm and found interesting phenomena: 1) the higher the temperature, the faster the nanofilaments grow; 2) the GAV-9 peptide formed double monolayers in a water nanofilm at 60℃, which further supports the hypothesis that the water nanofilm could change the hydrophobicity of mica. We believe these results can help not only the microcontact printing of amyloid peptides, but also a better understanding on how temperature controls the properties of water nanofilm.展开更多
The simultaneous detection of carcinoembryonic antigen(CEA)and microRNA-21(miR-21)is of significant clinical importance for cancer diagnosis,prognosis evaluation,and therapy monitoring.In this study,we developed a nov...The simultaneous detection of carcinoembryonic antigen(CEA)and microRNA-21(miR-21)is of significant clinical importance for cancer diagnosis,prognosis evaluation,and therapy monitoring.In this study,we developed a novel electrochemical biosensor utilizing a peptide-self-assembly-engineered signal amplification(PSA-e-SA)nanoarchitectonic strategy to achieve ultrasensitive and simultaneous quantification of these two critical biomarkers.By designing amphiphilic peptides(C_(16)-MB-AptamerCEA and C_(16)-Fc-ssDNA2)as multifunctional probes,the system exploits their dual roles in target recognition and signal amplification.These peptides self-assemble into nanostructures under mild conditions,facilitating enhanced loading of electroactive molecules such as methylene blue(MB)and ferrocene(Fc),thereby significantly amplifying the electrochemical signal.The biosensor achieved detection limits of 0.788 pM for CEA and 0.0357 nM for miR-21,demonstrating remarkable sensitivity enhancements of 18-fold and 3.8-fold compared to unamplified approaches.As a proof-of-concept study,further experiments underscored the excellent reproducibility and stability of the strategy while also demonstrating its applicability when tested with simulated serum samples.Thus,this work not only presents a valuable assay tool for early cancer diagnosis and biomarker analysis but also indicates that this signal amplification strategy based on peptide self-assembly engineering can be extended to detect other disease-related biomarkers,propelling the development of clinical applications for multifunctional biosensors.展开更多
Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sh...Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.展开更多
Biopolymer-driven supramolecular chirality in aqueous media has gained significant advancements in hierarchical chiral nanostructures.However,researches on the aqueous circularly polarized luminescence(CPL)induced by ...Biopolymer-driven supramolecular chirality in aqueous media has gained significant advancements in hierarchical chiral nanostructures.However,researches on the aqueous circularly polarized luminescence(CPL)induced by supramolecular selfassembly and its mechanism have been rarely reported.Herein,we explore the hierarchical chirality transfer in self-assembled fluorescent homopolypeptide systems showing aqueous CPL,and unveil anα-helix-dominated CPL regulation mechanism.A relationship is established between molecular structure(degree of polymerization,DP),supramolecular assembly(self-assembly temperature,T_(SA)),and resulting CPL properties.The stabilization for the homopolypeptideα-helix by increasing DP and decreasing T_(SA) enables efficient chirality transfer from the polypeptide backbone to its terminal chromophore,thereby improving CPL properties.Our work elucidates the critical role ofα-helix control in aqueous CPL systems,providing insights for designing biocompatible and tunable CPL-active nanomaterials.展开更多
CONSPECTUS:Controlling self-assembled peptide nanostructures has emerged as a significant area of research,offering versatile tools for developing functional materials for various applications.This Account emphasizes ...CONSPECTUS:Controlling self-assembled peptide nanostructures has emerged as a significant area of research,offering versatile tools for developing functional materials for various applications.This Account emphasizes the essential role of noncovalent interactions,particularly in peptide-based materials.Key forces,such as aromatic stacking and hydrogen bonding,are crucial for promoting molecular aggregation and stabilizing supramolecular structures.Numerous studies demonstrate how these interactions influence the phase transitions and the morphology of self-assembled structures.Recent advances in computational methodologies,including molecular dynamics simulations and machine learning,have significantly enhanced our understanding of self-assembly processes.These tools enable researchers to predict how molecular properties,such as hydrophobicity,charge distribution,and aromaticity,affect assembly behavior.Simulations uncover the energetic landscapes governing peptide aggregation,providing insights into the kinetic pathways and thermodynamic stabilities.Meanwhile,machine learning facilitates the rapid screening of peptide libraries,identifying sequences with optimal self-assembly characteristics,and accelerating material design with tailored functionalities.Beyond their structural and physicochemical properties,self-assembled peptide nanostructures hold immense potential in biological applications due to their versatility and biocompatibility.By manipulating molecular interactions,researchers have engineered responsive systems that interact with cellular environments to elicit specific biological responses.These peptide nanostructures can mimic extracellular matrices,facilitating cell adhesion,proliferation,and differentiation.They also show promise in modulating immune responses,recruiting immune cells,and regulating signaling pathways,making them valuable tools in immunotherapy and regenerative medicine.Moreover,their ability to disrupt bacterial membranes positions them as innovative alternatives to conventional antibiotics,addressing the urgent need for solutions to antimicrobial resistance.Despite its promise,peptide self-assembly faces several challenges.The assembly process is highly sensitive to environmental conditions,such as pH,temperature,and ionic strength,leading to variability in the morphology and properties.Furthermore,peptide aggregation can result in heterogeneous and poorly defined assemblies,complicating the reproducibility and scalability.Designing peptides with predictable self-assembly behavior remains a significant hurdle.Looking ahead,integrating computational predictions with experimental validations will be crucial in discovering novel peptide sequences with tailored self-assembly properties.Machine learning,combined with high-throughput screening techniques,will enable the rapid identification of optimal peptide sequences.In situ characterization tools,such as cryoelectron microscopy and advanced spectroscopy,will provide deeper insights into assembly mechanisms,aiding the rational design of peptide materials.As research progresses,the dynamic and reversible nature of noncovalent interactions can be leveraged to create adaptive responsive to environmental stimuli.Self-assembled peptide nanostructures are poised for impactful applications in biomedicine including targeted drug delivery,tissue repair,and advanced therapeutic strategies.Ultimately,these nanostructures represent a powerful platform for addressing complex challenges in biomedicine and beyond,paving the way for transformative breakthroughs in science and technology.展开更多
Nanostructures self-assembled by cross-β peptides with ordered structures and advantageous mechanical properties have many potential applications in biomaterials and nanotechnologies. Quantifying the intra-and inter-...Nanostructures self-assembled by cross-β peptides with ordered structures and advantageous mechanical properties have many potential applications in biomaterials and nanotechnologies. Quantifying the intra-and inter-molecular driving forces for peptide self-assembly at the atomistic level is essential for understanding the formation mechanism and nanomechanics of various morphologies of self-assembled peptides. We investigate the thermodynamics of the intra-and inter-sheet structure formations in the self-assembly process of cross-β peptide KⅢIK by means of steered molecular dynamics simulation combined with umbrella sampling. It is found that the mechanical properties of the intra-and inter-sheet structures are highly anisotropic with their intermolecular bond stiffness at the temperature of 300 K being 5.58 N/m and 0.32 N/m, respectively. This mechanical anisotropy comes from the fact that the intra-sheet structure is stabilized by enthalpy but the inter-sheet structure is stabilized by entropy. Moreover, the formation process of KⅢIK intra-sheet structure is cooperatively driven by the van der Waals （VDW） interaction between the hydrophobic side chains and the electrostatic interaction between the hydrophilic backbones, but that of the inter-sheet structure is primarily driven by the VDW interaction between the hydrophobic side chains. Although only peptide KⅢIK is studied, the qualitative conclusions on the formation mechanism should also apply to other cross-β peptides.展开更多
Effective countermeasures against multidrug-resistant nosocomial pathogens,such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA),require the development of innovative...Effective countermeasures against multidrug-resistant nosocomial pathogens,such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA),require the development of innovative antimicrobial strategies.This study presents a structure-function approach to antimicrobial peptide(AMP)design through the strategic integration of a cationic backbone with a hydrophobic core.This dual-domain architecture enables robust hydrophobic and electrostatic interactions,promoting spontaneous self-assembly and efficient membrane engagement.The lead peptide,Tryptolycin(TRPY),formed stable,monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity,with minimum inhibitory concentrations≤1μmol/L against multiple strains of MRSA and K.pneumoniae,while exerting minimal cytotoxicity toward mammalian cells.TRPY achieved rapid bacterial elimination,eradicating 99.9%of both planktonic and persister populations within minutes.Mechanistic investigations revealed that TRPY induced membrane permeabilization,promoted reactive oxygen species(ROS)production,and inhibited biofilm formation.In murine infection models,TRPY effectively eradicated established infections,reducing bacterial burden across target organs by 3-to 5-fold without significant cytotoxicity at therapeutic concentrations.Collectively,these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.展开更多
Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several...Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).展开更多
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.展开更多
Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments re...Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.展开更多
To synthesize KLD-12 peptide with sequence of AcN-KLDLKLDLKLDL-CNH2 and trigger its self-assembly in vitro, to encapsulate rabbit MSCs within peptide hydrogel for 3-D culture and to evaluate the feasibility of using i...To synthesize KLD-12 peptide with sequence of AcN-KLDLKLDLKLDL-CNH2 and trigger its self-assembly in vitro, to encapsulate rabbit MSCs within peptide hydrogel for 3-D culture and to evaluate the feasibility of using it as injectable scaffold for tissue engineering of IVD. KLD-12 peptide was purified and tested with high performance liquid chromatography （HPLC） and mass spectroscopy （MS）. KLD-12 peptide solutions with concentrations of 5 g/L, 2.5 g/L and 1 g/L were triggered to self-assembly with 1 xPBS in vitro, and the self-assembled peptide hydrogel was morphologically observed. Atomic force microscope （AFM） was employed to examine the inner structure of self-assembled peptide hydrogel. Mesenchymal stem cells （MSCs） were encapsulated within peptide hydrogel for 3-D culture for 2 weeks. Calcein-AM/PI fluorescence staining was used to detect living and dead cells. Cell viability was observed to evaluate the bioactivity of MSCs in KLD-12 peptide hydrogel. The results of HPLC and MS showed that the relative molecular mass of KLD-12 peptide was 1467.83, with a purity quotient of 95.36%. KLD-12 peptide at 5 g/L could self-assemble to produce a hydrogel, which was structurally integral and homogeneous and was able to provide sufficient cohesion to retain the shape of hydrogel. AFM demonstrated that the self-assembly of KLD-12 peptide hydrogel was successful and the assembled material was composed of a kind of nano-fiber with a diameter of 3040 nm and a length of hundreds of nm. Calcein-AM/PI fluorescence staining revealed that MSCs in KLD-12 peptide hydrogel grew well. Cell activity detection exhibited that the A value increased over the culture time. It is concluded that KLD-12 peptide was synthesized successfully and was able to self-assemble to produce nano-fiber hydrogel in vitro. MSCs in KLD-12 peptide hydrogel grew well and proliferated with the culture time. KLD-12 peptide hydrogel can serve as an excellent injectable material of biological scaffolds in tissue engineering of IVD.展开更多
Biomolecular self-assembly based on peptides and proteins is a general phenomenon encountered in natural and synthetic systems.Liquid–liquid phase separation(LLPS)is intimately involved in biomolecular self-assembly,...Biomolecular self-assembly based on peptides and proteins is a general phenomenon encountered in natural and synthetic systems.Liquid–liquid phase separation(LLPS)is intimately involved in biomolecular self-assembly,yet the key factors at a molecular scale activating or modulating such a process remain largely elusive.Herein,we discovered in our experiments that multistep desolvation is fundamental to the formation and evolution of peptide-rich droplets:The first step was partial desolvation of peptides to form peptide clusters,and the second step was selective desolvation of hydrophobic groups within clusters to trigger LLPS and the formation of peptiderich droplets,followed by complete desolvation of droplets,initiating the nucleation of peptide selfassembly.Manipulation of the degree of desolvation at different stages was an effective strategy to control the self-assembly pathways and polymorphisms.This study sheds light on the molecular origin of LLPS-mediated self-assembly distinct from classical one-step self-assembly and paves the way for the precise control of supramolecular self-assembly.展开更多
Peptide hydrogels have been widely used for diverse biomedical applications. However, our current understanding of the physical principles underlying the self-assembly process is still limited. In this review, we summ...Peptide hydrogels have been widely used for diverse biomedical applications. However, our current understanding of the physical principles underlying the self-assembly process is still limited. In this review, we summarize our current understanding on the physical chemistry principles from the basic interactions that drive the self-assembly process to the energy landscapes that dictate the thermodynamics and kinetics of the process. We discuss the effect of different factors that affect the kinetics of the self-assembly of peptide fibrils and how this is related to the macroscopic gelation process. We provide our understanding on the molecular origin of the complex and rugged energy landscape for the self-assembly of peptide hydrogels. The hierarchical self-assembled structures and the diverse self-assembling mechanism make it difficult and challenging to rationally design the physical and chemical properties of peptide hydrogels at the molecular revel. We also give our personal perspective to the potential future directions in this field.展开更多
A variety of nano-engineered photosensitizers have been developed for photodynamic therapy(PDT)of cancer diseases.However,traditional nano-engineering methods usually cannot avoid drug leakage and premature release,an...A variety of nano-engineered photosensitizers have been developed for photodynamic therapy(PDT)of cancer diseases.However,traditional nano-engineering methods usually cannot avoid drug leakage and premature release,and have disadvantages such as low drug load and inaccurate release.The self-assembly strategy based on amphiphilic peptides has been considered to be more attractive nano-engineering method.Here we developed novel acid-activatable self-assembled nanophotosensitizers based on an amphiphilic peptide derivative.The peptide derivative was synthesized from a fluorescein molecule with thermally activated delayed fluorescence(TADF).The self-assembled nanophotosensitizers can specifically enter the tumor cells and disassemble inside lysosomes companied with“turn-on”fluorescence and photodynamic therapy effect.Such smart nanophotosensitizers will open new opportunities for cancer theranostics.展开更多
PuraStat®is a novel self-assembling peptide(SAP)used as a haemostatic agent in endoscopy,with widespread application in surgical settings.While the current evidence,though deserving further expansion,demonstrates...PuraStat®is a novel self-assembling peptide(SAP)used as a haemostatic agent in endoscopy,with widespread application in surgical settings.While the current evidence,though deserving further expansion,demonstrates a good haemostatic performance profile for this substance,there remains significant heterogeneity among studies,and an analysis of this SAP as monotherapy is not always available.The recent study by Bellester et al in the World Journal of Gastrointestinal Endoscopy provided an optimal effectiveness profile of this SAP in 45 patients treated for gastrointestinal(GI)bleeding,particularly highlighting data on its use as monotherapy in upper GI bleeding.This invited article outlines the current evidence on PuraStat®and offers a commentary on the recently published study.展开更多
The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to s...The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.展开更多
基金Project supported by the National Basic Research Program of China(Grant No.2013CB932804)the National Natural Science Foundation of China(Grant Nos.91227115,11421063,11504431,and 21503275)+1 种基金the Fundamental Research Funds for Central Universities of China(Grant No.15CX02025A)the Application Research Foundation for Post-doctoral Scientists of Qingdao City,China(Grant No.T1404096)
文摘Besides our previous experimental discovery （Zhao Y R, et al. 2015 Langmuir, 31, 12975） that acetonitrile （ACN） can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK （KI4K） in aqueous solution, further experiments reported in this work demonstrate that ACN can also tune the mass of the self-assembled nanostructures. To understand the microscopic mechanism how ACN molecules interfere peptide self-assembly process, we conducted a series of molecular dynamics simulations on a monomer, a cross-β sheet structure, and a proto-fibril of KI4K in pure water, pure ACN, and ACN-water mixtures, respectively. The simulation results indicate that ACN enhances the intra-sheet interaction dominated by the hydrogen bonding （H-bonding） interactions between peptide backbones, but weakens the inter-sheet interaction dominated by the interactions between hydrophobic side chains. Through analyzing the correlations between different groups of solvent and peptides and the solvent behaviors around the proto-fibril, we have found that both the polar and nonpolar groups of ACN play significant roles in causing the opposite effects on intermolecular interactions among peptides. The weaker correlation of the polar group of ACN than water molecule with the peptide backbone enhances H-bonding interactions between peptides in the proto-fibril. The stronger correlation of the nonpolar group of ACN than water molecule with the peptide side chain leads to the accumulation of ACN molecules around the proto-fibril with their hydrophilic groups exposed to water, which in turn allows more water molecules close to the proto-fibril surface and weakens the inter-sheet interactions. The two opposite effects caused by ACN form a microscopic mechanism clearly explaining our experimental observations.
基金supported by the National Natural Science Foundation of China(Grant Nos.21373270 and 11504431)the Fundamental Research Funds for Central Universities of China(Grant No.15CX02025A)
文摘Under appropriate physicochemical conditions, short peptide fragments and their synthetic mimics have been shown to form elongated cross-fl nanostructures through self-assembly. The self-assembly process and the resultant peptide nanos- tructures are not only related to neurodegenerative diseases but also provide inspiration for the development of novel bionanomaterials. Both experimental and theoretical studies on peptide self-assembly have shown that the self-assembly process spans multiple time and length scales and is hierarchical, β-sheet self-assembly consists of three sub-processes from the microscopic to the mesoscopic level： β-sheet locking, lateral stacking, and morphological transformation. De- tailed atomistic simulation studies have provided insight into the early stages of peptide nanostructure formation and the interplay between different non-covalent interactions at the microscopic level. This review gives a brief introduction of the hierarchical peptide self-assembly process and focuses on the roles of various non-covalent interactions in the sub-processes based on recent simulation, experimental, and theoretical studies.
基金Funded by the National Natural Science Foundation of China(No.30500511)
文摘In order to study the biocompatibility of self-assembled FGL peptide nanofibers scaffold with neural stem cells （NSCs）, FGL pepitide-amphiphile （FGL-PA） was synthesized by solid-phase peptide synthesis technique. The diluted hydrochloric acid was added into FGL-PA solution to reduce the PH value and accordingly induce self-assembly. The morphological features of the assembled material were studied by transmission electron microscope. NSCs were cultured and added with self-assembled FGL-PA. CCK-8 kit was used to test its effect on the proliferation of NSCs. The differentiation of NSCs was also tested after FGL-PA assembled material added. The experimental results showed that FGL-PA could be self-assembled to form a hydrogel. TEM analysis showed the self-assembled hydrogel was nanofibers with diameter of 10-20 nm and length of hundreds nanometers. FGL-PA with concentrations of 50,100, or 200 mg/L could promote the proliferation of NSCs, and absorbance of them was increased （P〈0.05）. The rate of neurons differentiated from NSCs was improved greatly by FGL-PA assembled material compared with control （P〈0.05）. The findings suggested that FGL-PA could self-assemble to nanofiber hydrogel, which had good biocompatibility with NSCs.
基金Supported by grants from the National Natural Science Foundation of China(Nos.21171086 and 81160213)Inner Mongolia Grassland Talent(No.108-108038)+1 种基金Inner Mongolia Autonomous Region Natural Science Foundation(No.2013MS1121)the Inner Mongolia Agricultural University(Nos.211-109003 and 211-206038)
文摘Peptide GAV-9 is derived from 3 different disease related proteins. The self-assembly of GAV-9 in a water nanofilm attracted much attention recently. We studied how the temperature factor influenced the peptide selfassembly in a water nanofilm and found interesting phenomena: 1) the higher the temperature, the faster the nanofilaments grow; 2) the GAV-9 peptide formed double monolayers in a water nanofilm at 60℃, which further supports the hypothesis that the water nanofilm could change the hydrophobicity of mica. We believe these results can help not only the microcontact printing of amyloid peptides, but also a better understanding on how temperature controls the properties of water nanofilm.
基金the National Natural Science Foundation of China(Nos.22004051 and 22072060)the Natural Science Foundation of Jiangsu Province(No.BK20180858)+4 种基金the China Postdoctoral Science Foundation(No.2019M661733)the Scientific Research Starting Foundation for Senior Talent at Jiangsu University(No.18JDG025)Science Foundation of Wuxi Health Committee(No.BJ202220)Top Talent Support Program for young and middle-aged people of WuxiHealth Committee(No.BJ2023105)Opening of Jiangsu Provincial Key Laboratory of Laboratory Medicine(No.JSKLM-T-2024-1).
文摘The simultaneous detection of carcinoembryonic antigen(CEA)and microRNA-21(miR-21)is of significant clinical importance for cancer diagnosis,prognosis evaluation,and therapy monitoring.In this study,we developed a novel electrochemical biosensor utilizing a peptide-self-assembly-engineered signal amplification(PSA-e-SA)nanoarchitectonic strategy to achieve ultrasensitive and simultaneous quantification of these two critical biomarkers.By designing amphiphilic peptides(C_(16)-MB-AptamerCEA and C_(16)-Fc-ssDNA2)as multifunctional probes,the system exploits their dual roles in target recognition and signal amplification.These peptides self-assemble into nanostructures under mild conditions,facilitating enhanced loading of electroactive molecules such as methylene blue(MB)and ferrocene(Fc),thereby significantly amplifying the electrochemical signal.The biosensor achieved detection limits of 0.788 pM for CEA and 0.0357 nM for miR-21,demonstrating remarkable sensitivity enhancements of 18-fold and 3.8-fold compared to unamplified approaches.As a proof-of-concept study,further experiments underscored the excellent reproducibility and stability of the strategy while also demonstrating its applicability when tested with simulated serum samples.Thus,this work not only presents a valuable assay tool for early cancer diagnosis and biomarker analysis but also indicates that this signal amplification strategy based on peptide self-assembly engineering can be extended to detect other disease-related biomarkers,propelling the development of clinical applications for multifunctional biosensors.
基金supported by the National Basic Research Program of China 973 Program(Nos.2021YFA0910803,2021YFC2103900)the National Natural Science Foundation of China(No.21977011)+4 种基金the Natural Science Foundation of Guangdong Province(Nos.2022A1515010996 and 2020A1515011544)the Shenzhen Science and Technology Innovation Committee(Nos.RCJC20200714114433053,JCYJ20180507181527112 and JCYJ20200109140406047)the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(No.2019SHIBS0004)the Shenzhen Fundamental Research Program(No.GXWD20201231165807007–20200827170132001)Tian Fu Jin Cheng Laboratory(Advanced Medical Center)Group Racing Project(No.TFJC2023010008)。
文摘Developing novel building blocks with predictable side-chain orientations and minimal intramolecular interactions is essential for peptide-based self-assembling materials.Traditional structures likeα-helices andβ-sheets rely on such interactions for stability,limiting control over exposed interacting moieties.Here,we reported a novel,frame-like peptide scaffold that maintains exceptional stability without intramolecular interactions.This structure exposes its backbone and orients side chains for hierarchical self-assembly into micron-scale cubes.By introducing mutations at specific sites,we controlled packing orientations,offering new options for tunable self-assembly.Our scaffold provides a versatile platform for designing advanced peptide materials,with applications in nanotechnology and biomaterials.
基金supported by the National Key Research and Development Program of China(2023YFB3810001)the National Natural Science Foundation of China(52333007 and 52273197)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(2023A1515011004)the Shenzhen Key Laboratory of Functional Aggregate Materials(ZDSYS20211021111400001)the Science Technology Innovation Commission of Shenzhen Municipality(GJHZ20210705141810031,KQTD20210811090142053,and JCYJ20220818103007014)the Innovation and Technology Commission of Hong Kong(ITC-CNERC14SC01).
文摘Biopolymer-driven supramolecular chirality in aqueous media has gained significant advancements in hierarchical chiral nanostructures.However,researches on the aqueous circularly polarized luminescence(CPL)induced by supramolecular selfassembly and its mechanism have been rarely reported.Herein,we explore the hierarchical chirality transfer in self-assembled fluorescent homopolypeptide systems showing aqueous CPL,and unveil anα-helix-dominated CPL regulation mechanism.A relationship is established between molecular structure(degree of polymerization,DP),supramolecular assembly(self-assembly temperature,T_(SA)),and resulting CPL properties.The stabilization for the homopolypeptideα-helix by increasing DP and decreasing T_(SA) enables efficient chirality transfer from the polypeptide backbone to its terminal chromophore,thereby improving CPL properties.Our work elucidates the critical role ofα-helix control in aqueous CPL systems,providing insights for designing biocompatible and tunable CPL-active nanomaterials.
基金supported by the National Natural Science Foundation of China(82272145)and the Foundation of Westlake University.
文摘CONSPECTUS:Controlling self-assembled peptide nanostructures has emerged as a significant area of research,offering versatile tools for developing functional materials for various applications.This Account emphasizes the essential role of noncovalent interactions,particularly in peptide-based materials.Key forces,such as aromatic stacking and hydrogen bonding,are crucial for promoting molecular aggregation and stabilizing supramolecular structures.Numerous studies demonstrate how these interactions influence the phase transitions and the morphology of self-assembled structures.Recent advances in computational methodologies,including molecular dynamics simulations and machine learning,have significantly enhanced our understanding of self-assembly processes.These tools enable researchers to predict how molecular properties,such as hydrophobicity,charge distribution,and aromaticity,affect assembly behavior.Simulations uncover the energetic landscapes governing peptide aggregation,providing insights into the kinetic pathways and thermodynamic stabilities.Meanwhile,machine learning facilitates the rapid screening of peptide libraries,identifying sequences with optimal self-assembly characteristics,and accelerating material design with tailored functionalities.Beyond their structural and physicochemical properties,self-assembled peptide nanostructures hold immense potential in biological applications due to their versatility and biocompatibility.By manipulating molecular interactions,researchers have engineered responsive systems that interact with cellular environments to elicit specific biological responses.These peptide nanostructures can mimic extracellular matrices,facilitating cell adhesion,proliferation,and differentiation.They also show promise in modulating immune responses,recruiting immune cells,and regulating signaling pathways,making them valuable tools in immunotherapy and regenerative medicine.Moreover,their ability to disrupt bacterial membranes positions them as innovative alternatives to conventional antibiotics,addressing the urgent need for solutions to antimicrobial resistance.Despite its promise,peptide self-assembly faces several challenges.The assembly process is highly sensitive to environmental conditions,such as pH,temperature,and ionic strength,leading to variability in the morphology and properties.Furthermore,peptide aggregation can result in heterogeneous and poorly defined assemblies,complicating the reproducibility and scalability.Designing peptides with predictable self-assembly behavior remains a significant hurdle.Looking ahead,integrating computational predictions with experimental validations will be crucial in discovering novel peptide sequences with tailored self-assembly properties.Machine learning,combined with high-throughput screening techniques,will enable the rapid identification of optimal peptide sequences.In situ characterization tools,such as cryoelectron microscopy and advanced spectroscopy,will provide deeper insights into assembly mechanisms,aiding the rational design of peptide materials.As research progresses,the dynamic and reversible nature of noncovalent interactions can be leveraged to create adaptive responsive to environmental stimuli.Self-assembled peptide nanostructures are poised for impactful applications in biomedicine including targeted drug delivery,tissue repair,and advanced therapeutic strategies.Ultimately,these nanostructures represent a powerful platform for addressing complex challenges in biomedicine and beyond,paving the way for transformative breakthroughs in science and technology.
基金Project supported by the National Basic Research Program of China(Grant No.2013CB932804)the National Natural Science Foundation of China(Grant Nos.11421063,11647601,11504431,and 21503275)+1 种基金the Scientific Research Foundation of China University of Petroleum(East China)for Young Scholar(Grant Y1304073)financial support through the CAS Biophysics Interdisciplinary Innovation Team Project(Grant No.2060299)
文摘Nanostructures self-assembled by cross-β peptides with ordered structures and advantageous mechanical properties have many potential applications in biomaterials and nanotechnologies. Quantifying the intra-and inter-molecular driving forces for peptide self-assembly at the atomistic level is essential for understanding the formation mechanism and nanomechanics of various morphologies of self-assembled peptides. We investigate the thermodynamics of the intra-and inter-sheet structure formations in the self-assembly process of cross-β peptide KⅢIK by means of steered molecular dynamics simulation combined with umbrella sampling. It is found that the mechanical properties of the intra-and inter-sheet structures are highly anisotropic with their intermolecular bond stiffness at the temperature of 300 K being 5.58 N/m and 0.32 N/m, respectively. This mechanical anisotropy comes from the fact that the intra-sheet structure is stabilized by enthalpy but the inter-sheet structure is stabilized by entropy. Moreover, the formation process of KⅢIK intra-sheet structure is cooperatively driven by the van der Waals （VDW） interaction between the hydrophobic side chains and the electrostatic interaction between the hydrophilic backbones, but that of the inter-sheet structure is primarily driven by the VDW interaction between the hydrophobic side chains. Although only peptide KⅢIK is studied, the qualitative conclusions on the formation mechanism should also apply to other cross-β peptides.
基金supported by the National Key Research and Development Program of China(2022YFC2105003,2022YFC2602500)National Natural Science Foundation of China(92469103,32400769,32300404)+6 种基金Chinese Academy of Sciences(YSBR-111,SAJC202402)Yunnan Provincial Science and Technology Department(202305AH340007,202301AT070343,202502AA310005)Yunnan Characteristic Plant Extraction Laboratory(2025YKZY002)Kunming Science and Technology Bureau(2022SCP007)New Cornerstone Investigator Program from Shenzhen New Cornerstone Science Foundation(NCI202238)Tianfu Jincheng Laboratory Foundation(TFJC2023010007)Chinese Academy of Sciences and World Academy of Sciences(CAS-TWAS)President’s Fellowship Program(2019A8010415001)。
文摘Effective countermeasures against multidrug-resistant nosocomial pathogens,such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA),require the development of innovative antimicrobial strategies.This study presents a structure-function approach to antimicrobial peptide(AMP)design through the strategic integration of a cationic backbone with a hydrophobic core.This dual-domain architecture enables robust hydrophobic and electrostatic interactions,promoting spontaneous self-assembly and efficient membrane engagement.The lead peptide,Tryptolycin(TRPY),formed stable,monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity,with minimum inhibitory concentrations≤1μmol/L against multiple strains of MRSA and K.pneumoniae,while exerting minimal cytotoxicity toward mammalian cells.TRPY achieved rapid bacterial elimination,eradicating 99.9%of both planktonic and persister populations within minutes.Mechanistic investigations revealed that TRPY induced membrane permeabilization,promoted reactive oxygen species(ROS)production,and inhibited biofilm formation.In murine infection models,TRPY effectively eradicated established infections,reducing bacterial burden across target organs by 3-to 5-fold without significant cytotoxicity at therapeutic concentrations.Collectively,these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
文摘Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
基金the National Natural Science Foundation of China(No.21921003 for Z.T.L.and 22201293 for S.B.Y.)Shanghai Sailing Program(No.22YF1458300 for S.B.Y.)for financial support。
文摘Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.
基金supported by a"863"Key Project of the High Technology Research and Development Program of China(No.2006AA02A124)
文摘To synthesize KLD-12 peptide with sequence of AcN-KLDLKLDLKLDL-CNH2 and trigger its self-assembly in vitro, to encapsulate rabbit MSCs within peptide hydrogel for 3-D culture and to evaluate the feasibility of using it as injectable scaffold for tissue engineering of IVD. KLD-12 peptide was purified and tested with high performance liquid chromatography （HPLC） and mass spectroscopy （MS）. KLD-12 peptide solutions with concentrations of 5 g/L, 2.5 g/L and 1 g/L were triggered to self-assembly with 1 xPBS in vitro, and the self-assembled peptide hydrogel was morphologically observed. Atomic force microscope （AFM） was employed to examine the inner structure of self-assembled peptide hydrogel. Mesenchymal stem cells （MSCs） were encapsulated within peptide hydrogel for 3-D culture for 2 weeks. Calcein-AM/PI fluorescence staining was used to detect living and dead cells. Cell viability was observed to evaluate the bioactivity of MSCs in KLD-12 peptide hydrogel. The results of HPLC and MS showed that the relative molecular mass of KLD-12 peptide was 1467.83, with a purity quotient of 95.36%. KLD-12 peptide at 5 g/L could self-assemble to produce a hydrogel, which was structurally integral and homogeneous and was able to provide sufficient cohesion to retain the shape of hydrogel. AFM demonstrated that the self-assembly of KLD-12 peptide hydrogel was successful and the assembled material was composed of a kind of nano-fiber with a diameter of 3040 nm and a length of hundreds of nm. Calcein-AM/PI fluorescence staining revealed that MSCs in KLD-12 peptide hydrogel grew well. Cell activity detection exhibited that the A value increased over the culture time. It is concluded that KLD-12 peptide was synthesized successfully and was able to self-assemble to produce nano-fiber hydrogel in vitro. MSCs in KLD-12 peptide hydrogel grew well and proliferated with the culture time. KLD-12 peptide hydrogel can serve as an excellent injectable material of biological scaffolds in tissue engineering of IVD.
基金supported by the National Science Fund for Distinguished Young Scholars of China(grant no.22025207)National Natural Science Foundation of China(grant nos.22172172 and 22232006)+3 种基金Youth Innovation Promotion Association of CAS(grant no.2022049)China Scholarship Council(CSC,grant no.202104910187)IPE Project for Frontier Basic Research(grant no.QYJC-2022-011)Natural Science Foundation of Hebei Province(grant nos.B2020103036 and B2020103025).
文摘Biomolecular self-assembly based on peptides and proteins is a general phenomenon encountered in natural and synthetic systems.Liquid–liquid phase separation(LLPS)is intimately involved in biomolecular self-assembly,yet the key factors at a molecular scale activating or modulating such a process remain largely elusive.Herein,we discovered in our experiments that multistep desolvation is fundamental to the formation and evolution of peptide-rich droplets:The first step was partial desolvation of peptides to form peptide clusters,and the second step was selective desolvation of hydrophobic groups within clusters to trigger LLPS and the formation of peptiderich droplets,followed by complete desolvation of droplets,initiating the nucleation of peptide selfassembly.Manipulation of the degree of desolvation at different stages was an effective strategy to control the self-assembly pathways and polymorphisms.This study sheds light on the molecular origin of LLPS-mediated self-assembly distinct from classical one-step self-assembly and paves the way for the precise control of supramolecular self-assembly.
基金financially supported by the National Natural Science Foundation of China(Nos.21522402 and 11304156)the Fundamental Research Funds for the Central Universities(Nos.020414380070,020414380050 and 020414380058)
文摘Peptide hydrogels have been widely used for diverse biomedical applications. However, our current understanding of the physical principles underlying the self-assembly process is still limited. In this review, we summarize our current understanding on the physical chemistry principles from the basic interactions that drive the self-assembly process to the energy landscapes that dictate the thermodynamics and kinetics of the process. We discuss the effect of different factors that affect the kinetics of the self-assembly of peptide fibrils and how this is related to the macroscopic gelation process. We provide our understanding on the molecular origin of the complex and rugged energy landscape for the self-assembly of peptide hydrogels. The hierarchical self-assembled structures and the diverse self-assembling mechanism make it difficult and challenging to rationally design the physical and chemical properties of peptide hydrogels at the molecular revel. We also give our personal perspective to the potential future directions in this field.
基金financially supported by the National Natural Science Foundation of China(No.21877011)the Fundamental Research Funds for the Central Universities(No.DUT20YG119)the Talent Fund of Shandong Collaborative Innovation Center of Eco-Chemical Engineering(No.XTCXYX03)。
文摘A variety of nano-engineered photosensitizers have been developed for photodynamic therapy(PDT)of cancer diseases.However,traditional nano-engineering methods usually cannot avoid drug leakage and premature release,and have disadvantages such as low drug load and inaccurate release.The self-assembly strategy based on amphiphilic peptides has been considered to be more attractive nano-engineering method.Here we developed novel acid-activatable self-assembled nanophotosensitizers based on an amphiphilic peptide derivative.The peptide derivative was synthesized from a fluorescein molecule with thermally activated delayed fluorescence(TADF).The self-assembled nanophotosensitizers can specifically enter the tumor cells and disassemble inside lysosomes companied with“turn-on”fluorescence and photodynamic therapy effect.Such smart nanophotosensitizers will open new opportunities for cancer theranostics.
文摘PuraStat®is a novel self-assembling peptide(SAP)used as a haemostatic agent in endoscopy,with widespread application in surgical settings.While the current evidence,though deserving further expansion,demonstrates a good haemostatic performance profile for this substance,there remains significant heterogeneity among studies,and an analysis of this SAP as monotherapy is not always available.The recent study by Bellester et al in the World Journal of Gastrointestinal Endoscopy provided an optimal effectiveness profile of this SAP in 45 patients treated for gastrointestinal(GI)bleeding,particularly highlighting data on its use as monotherapy in upper GI bleeding.This invited article outlines the current evidence on PuraStat®and offers a commentary on the recently published study.
基金supported by the National Natural Science Foundation of China(81971733,31771085 and 81722026)the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M3e022,China)+1 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018RC350016 and 2018PT35031,China)the Science Foundation for Distinguished Young Scholars of Tianjin(18JCJQJC47300 and 19JCJQJC62200,China)
文摘The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.
