Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the del...Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.展开更多
Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differe...Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.展开更多
Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to t...Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.展开更多
Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumve...Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumvent MDR in C6 glioma cells.The physiochemical properties including particle size,encapsulation efficiency and morphology were evaluated in vitro.Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells.The cytotoxicity of the BOR/PTX LANs was determined by MTT assay.After that,the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis.BOR/PTX LANs have a higher entrapment efficiency(90.4±1.2%),small particle size(107.5±3.2 nm),narrow distribution(P.I.=0.171±0.02).The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipidalbumin nanoassemblies(PTX LANs)in quantitative research.The result was further confirmed by confocal laser scanning microscopy qualitatively.The cellular uptake was energy-,timeand concentration-dependent,and clathrin-and endosome/lysosome-associated pathways were involved.The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol.Moreover,the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues,demonstrating the tumor targeted ability of BOR/PTX LANs.These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition,and shown the potential for treatment of gliomas.展开更多
Chemotherapy has been recommended as the standard protocol for triple-negative breast cancer(TNBC)at the advanced stage.However,the current treatment is unsatisfactory due to inefficient drug accumulation and rapid ch...Chemotherapy has been recommended as the standard protocol for triple-negative breast cancer(TNBC)at the advanced stage.However,the current treatment is unsatisfactory due to inefficient drug accumulation and rapid chemo-resistance.Thus,rational design of advanced drug delivery systems that can induce multiple cell death pathways is a promising strategy to combat TNBC.Ferroptosis is a powerful non-apoptotic cell death modality,showing potential in tumor inhibition.Herein,we propose a binary prodrug nanoassemblies that combines chemotherapy with ferroptosis for TNBC treatment.In this system,paclitaxel is linked with paracetamol(ferroptosis activator)by a disulfide linkage to construct self-assembly prodrug.Meanwhile,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-methyl(polyethylene glycol)-2000-tyrosine(DSPE-PEG2k-tyrosine)is applied for large neutral amino acid transporter 1(LAT1)targeting,which is highly expressed in TNBC.The prodrug nanoassemblies exhibit good stability and a glutathione(GSH)-responsive release profile.Furthermore,the LAT1-targeted nanoassemblies show stronger cytotoxicity,higher cellular uptake,and more obvious ferroptosis activation than non-decorated ones.In a TNBC mice model,the prodrug nanoassemblies demonstrate strong anti-tumor efficacy.The application of ferroptosis-assisting chemotherapy may provide a promising strategy for TNBC therapy.展开更多
Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, th...Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-ofconcept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation,we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug interaction.Furthermore, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.展开更多
As a representative type of self-supported templates, cyano-bridged cyanogels provide ideal plateaus for synthesis of three-dimensional(3 D) nanostructures. Herein, 3 D pomegranate-like Fe-doped NiCo nanoassemblies(3 ...As a representative type of self-supported templates, cyano-bridged cyanogels provide ideal plateaus for synthesis of three-dimensional(3 D) nanostructures. Herein, 3 D pomegranate-like Fe-doped NiCo nanoassemblies(3 D PG-NiCoFe NAs) were synthesized via facile one-step bi-component cyanogel reduction with NaBH_4 as the reducing agent. Specifically, the influence of the incorporated Fe amount was carefully investigated by finely adjusting the feeding molar ratios of the Ni/Co/Fe atoms in the precursors.By virtue of the unique structure and enriched oxygen vacancies originated from well-modulated electronic structures, the 3 D PG-NiCoFe-211 NAs exhibited outstanding electrocatalytic performances for oxygen evolution reaction(OER) in alkaline solution, outperforming commercial RuO_2 catalyst. The current incorporation of foreign metal atom into host material provides some valuable insights into design and synthesis of metal-based nanocatalysts for constructing practical water splitting devices.展开更多
In this paper, cucurbit[7]uril(CB[7])-mediated three-dimensional gold nanoassemblies were successfully prepared to increase the loaded amount of CB[7] and enhance the electrochemical detection of amino acids. Particle...In this paper, cucurbit[7]uril(CB[7])-mediated three-dimensional gold nanoassemblies were successfully prepared to increase the loaded amount of CB[7] and enhance the electrochemical detection of amino acids. Particle sizes of gold nanoparticles(Au NPs) significantly affect stability and detection sensitivity of nanoassemblies. The volume of gold nanoassemblies first increased and then decreased with the increase of CB[7] concentration. The 3D gold nanoassemblies composed of 16 nm Au NPs and 100 μmol/L CB[7]had excellent stability and maximum volume, exhibiting more sensitive detection for a variety of amino acids. And the detection limits of aromatic amino acids are lower in virtue of the higher binding constant between aromatic amino acids and CB[7]. This study will develop and deepen our understanding of molecular recognition in amino acids detection.展开更多
Oxaliplatin(OXA)has shown excellent potential in inducing immunogenic cell death and enhancing immunotherapy.However,the poor physicochemical properties of oxaliplatin make it difficult to achieve efficient synchronou...Oxaliplatin(OXA)has shown excellent potential in inducing immunogenic cell death and enhancing immunotherapy.However,the poor physicochemical properties of oxaliplatin make it difficult to achieve efficient synchronous delivery and synergistic immunotherapy with immune checkpoint inhibitors.To address this,we designed structurally optimized dual-wing butterfly prodrugs:oxaliplatin prodrug(POP)that enhances immunogenicity and reducible NLG919 homodimer(NSSN)that mitigates immunosuppression.Structural optimization of dual-wing butterfly prodrugs significantly enhanced lipid solubility compared to the parent drugs.It is worth noting that we assembled two dual-wing butterfly prodrugs,POP and NSSN,together into hybrid nanoassemblies(NAs),achieving advantages such as stable assembly,flexible dosing,and collaborative therapy.Dual-wing butterfly prodrug-driven hybrid NAs demonstrated enhanced antitumor efficacy and metastasis control in experimental models,with biocompatibility confirmed through biosafety evaluations.This work proposes a co-delivery strategy based on dual-wing butterfly prodrugs as a clinically translatable candidate.展开更多
The clinical utility of irinotecan is restricted by individual variability in carboxylesterase expression.Direct administration of its active metabolite,7-ethyl-10-hydroxycamptothecin(SN38),presents an appealing alter...The clinical utility of irinotecan is restricted by individual variability in carboxylesterase expression.Direct administration of its active metabolite,7-ethyl-10-hydroxycamptothecin(SN38),presents an appealing alternative due to its potent anti-tumor efficacy.However,the undesirable properties of SN38,such as poor water solubility and nontarget toxicity,present significant hurdles to its clinical development.Prodrug nanoassemblies based on modular design strategy show promise in overcoming these challenges by enhancing drug delivery and selective activation.In modular design,the modification module plays a crucial role in improving the self-assembly capability of prodrugs.While current studies mainly focus on using straight aliphatic chains for prodrug design,branched aliphatic chains emerge as superior alternatives warranting further investigation.In this study,we selected 2-heptylundecanol(BAlc18)as modification module to construct an SN38 prodrug.Through exquisite design,SN38-SS-BAlc18 NPs integrated prominent properties in selfassembly capability,specific activation and biocompatibility,resolving the challenges of irinotecan and SN38,ultimately demonstrating excellent anti-tumor efficacy.This exploration enriched the design theory of prodrug nanoassemblies that can effectively balance safety and colorectal anti-tumor efficacy.展开更多
Irinotecan,one of the most effective chemotherapeutic agents for the treatment of advanced colorectal cancer,suffers from extremely low activatability and non-selective tumor activation.7-Ethyl-10-hydroxy-camptothecin...Irinotecan,one of the most effective chemotherapeutic agents for the treatment of advanced colorectal cancer,suffers from extremely low activatability and non-selective tumor activation.7-Ethyl-10-hydroxy-camptothecin(SN38),the active metabolite of irinotecan,has been limited in clinical development due to poor water solubility and stability.Here,the thioether bond and disulfide bond were employed as response modules to construct tumor-selective SN38 prodrug nanoassemblies(SN38-S-C_(21) NPs and SN38-SS-C_(21) NPs).11-Henicosanol was chosen as a self-assembly module to enhance stability.Both SN38-S-C_(21) NPs and SN38-SS-C_(21) NPs presented ultra-high in vivo stability with a 12146-fold and 23151-fold elevation in the area under the curve(AUC)compared to SN38.Moreover,SN38-S-C_(21) NPs and SN38-SS-C_(21) NPs showed a significant reduction of SN38exposure in blood compared to irinotecan.Importantly,the prodrug nanoassemblies enabled selective activation within tumor cells,and the conversion rates of SN38-SS-C_(21) NPs and SN38-S-C_(21) NPs to SN38 were 10-and 7-fold higher than irinotecan.Compared with SN38-S-C_(21) NPs,the superior in vivo stability,SN38 conversion efficiency and tumor selectivity of SN38-SSC_(21) NPs resulted in potent antitumor effects and safety.Our findings proved that the disulfide bond was more suitable for constructing high-performance SN38 prodrug nanoassemblies,which showed significant promise for the rational design of SN38 nanomedicines.展开更多
Prodrug-based nanoassemblies have emerged as advanced carrier-free nanomedicines.These prodrugs typically consist of drug modules,response modules,and modification modules.The general role of modification modules is t...Prodrug-based nanoassemblies have emerged as advanced carrier-free nanomedicines.These prodrugs typically consist of drug modules,response modules,and modification modules.The general role of modification modules is to modulate the self-assembly ability of the prodrugs.How to optimize the structure of modification modules for balanced efficacy and safety of high-toxicity chemotherapeutic drugs deserves to be further investigated.In this study,a modification strategy of aliphatic alcohols with various chain lengths(SC_(4),SC_(8),SC_(12),SC_(16) and SC_(20))was carried out to design five cabazitaxel(CBZ)prodrugs.Among them,CBZ-SC NPs with shorter chain length(SC_(4) and SC_(8))showed poor self-assembly stability.CBZ-SC_(12) NPs also failed to remain stable while the other two CBZ-SC NPs exhibited good stability.In turn,the drug release rate was hindered by the increasing chain length.CBZ-SC_(12) NPs caused kidney damage due to their high redox-sensitivity and rapid release rate during circulation.By contrast,CBZ-SC NPs with longer chain length(SC_(16) and SC_(20))not only demonstrated superior stability with improved pharmacokinetic behavior,but also might solve the dilemma of dose-related toxicity caused by CBZ.Overall,these findings emphasized the importance of chain length in modification module to modulate the efficacy and safety of CBZ prodrug nanoassemblies.展开更多
Dimeric prodrug nanoassemblies(DPNAs)offer great potential in improving the efficacy of chemotherapy.Previously,we developed tetrasulfide bonds as a novel response module and the obtainedγ-4S-2CTX NPs demonstrated su...Dimeric prodrug nanoassemblies(DPNAs)offer great potential in improving the efficacy of chemotherapy.Previously,we developed tetrasulfide bonds as a novel response module and the obtainedγ-4S-2CTX NPs demonstrated superlative self-assembly stability and enhanced anti-tumor efficacy.However,current DPNAs mainly rely on simple PEGylation for surface modification to improve blood circulation,which lacks tumor-selective functionality and limits their further application.To address these limitations,we introduced a new surface modification strategy using RM-1 tumor cell membranes(CMs)to enhance biofunctionality.The initial attempt to use CMs as a single surface modification failed because the affinity of nanocores-CMs remains a problem,which affected the stability of membrane-coated DPNAs.To address this,we used 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-2000](DSPE-PEG2k)as an adhesive bridge to improve the affinity between CMs and DPNAs,resulting in a dual-modified formulation termed CM-pDPNAs.This dual modification strategy enhanced CMs binding to DPNAs,enabling precise tumor recognition and internalization,thereby improving tumor elimination efficacy.Furthermore,this approach addressed key challenges associated with current CM-coated nanoparticles(CM-NPs),including complex preparation procedures and poor drug-carrier compatibility.This work elucidates the application of CMs as surface modification modules,paving the way for the next generation of biomimetic prodrug nanoassemblies with superior stability and tumor specficity.展开更多
Fengxiang Liu1,,Rongzheng Liu1,,Xiaoyuan Fan2,,Xia Wang2,,Kaiyuan Wang1,,Hainan Zhao3,,Hao Ye4,Shunzhe Zheng1,Xiao Kuang1,Yinxian Yang1,Haotian Zhang5,Qiming Kan5,Zhonggui He1,6,Jian Chen 7,and Jin Sun1,61 Department ...Fengxiang Liu1,,Rongzheng Liu1,,Xiaoyuan Fan2,,Xia Wang2,,Kaiyuan Wang1,,Hainan Zhao3,,Hao Ye4,Shunzhe Zheng1,Xiao Kuang1,Yinxian Yang1,Haotian Zhang5,Qiming Kan5,Zhonggui He1,6,Jian Chen 7,and Jin Sun1,61 Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China 2 School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China 3 Nephrology department,The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China 4 Multi-Scale Robotics Lab(MSRL),Institute of Robotics&Intelligent Systems(IRIS),ETH Zurich 8092,Switzerland 5 School of Life Science and Biopharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China 6 Joint International Research Laboratory of Intelligent Drug Delivery Systems,Ministry of Education,Shenyang 110016,China 7 School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China§Fengxiang Liu,Rongzheng Liu,Xiaoyuan Fan,Xia Wang,Kaiyuan Wang,and Hainan Zhao contributed equally to this work.展开更多
In the originally published version of this article,the authors identified inadvertent errors in the preparation of Fig.7A and B.During assembly of the figure,incorrect images from the same batch of raw data were mist...In the originally published version of this article,the authors identified inadvertent errors in the preparation of Fig.7A and B.During assembly of the figure,incorrect images from the same batch of raw data were mistakenly selected and duplicated across two separate studies.The figure has now been replaced with the correct images sourced from the same original dataset.展开更多
Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reac...Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reactive oxygen species(ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid(LA) and docetaxel(DTX). This mono thioether-linked conjugates(DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve(AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4 T1 xenograft. It turned out this nanoassemblies couldenhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.展开更多
Novel self-assembled architectures have received a growing amount of attention and have significant potential for application in catalysis/electrocatalysis. Herein, we take advantage of the unique coordination and sel...Novel self-assembled architectures have received a growing amount of attention and have significant potential for application in catalysis/electrocatalysis. Herein, we take advantage of the unique coordination and self-assembly properties of arginine for the preparation of dendritic PtCu bimetallic nanoassemblies with tunable chemical composition and structure. Strong interactions between the arginine molecules are key in driving the self-assembly of primary nanocrystals. In addition, the strong coordination interactions between arginine and metal ions is responsible for the formation of Pt-Cu alloys. We also investigated the electrocatalytic activity of various dendritic PtCu bimetallic nanoassemblies towards the methanol oxidation reaction. PtBCUl nanoassemblies exhibited excellent electrocatalytic activity and stability in comparison with other PtCu bimetallic nanoassemblies （PtlCu3, PtlCu~） and commercial Pt black, due to their unique dendritic structures and the synergistic effect between the Pt and Cu atoms.展开更多
Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis;however,the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells.Here,we repor...Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis;however,the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells.Here,we report reactive oxygen species(ROS)-responsive and size-reducible nanoassemblies,formed by multivalent host-vip interactions betweenβ-cyclodextrins(β-CD)-anchored discoidal recombinant high-density lipoprotein(NP^(3)_(ST))and hyaluronic acid-ferrocene(HA-Fc)conjugates.The HA-Fc/NP^(3)_(ST)nanoassemblies have extended blood circulation time,specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium,rapidly disassemble in response to excess ROS in the intimal and release smaller NP^(3)_(ST),allowing for further plaque penetration,macrophage-targeted cholesterol efflux and drug delivery.In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP^(3)_(ST)reduces plaque size by 53%,plaque lipid deposition by 63%,plaque macrophage content by 62%and local inflammatory factor level by 64%compared to the saline group.Meanwhile,HA-Fc/NP^(3)_(ST)alleviates systemic inflammation characterized by reduced serum inflammatory factor levels.Collectively,HA-Fc/NP^(3)_(ST)nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability,thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.展开更多
Poly（caprolactone-b-2-vinylpyridine） （PCL-P2VP） coated with folate-conjugated M13 （FA-M13） provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin ...Poly（caprolactone-b-2-vinylpyridine） （PCL-P2VP） coated with folate-conjugated M13 （FA-M13） provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin （DOX）. The DOXqoaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.展开更多
Controllable self-assembly of noble metal nanocrystals is of broad interest for the development of highly active electrocatalysts. Here we report an efficient arginine-mediated hydrothermal approach for the high-yield...Controllable self-assembly of noble metal nanocrystals is of broad interest for the development of highly active electrocatalysts. Here we report an efficient arginine-mediated hydrothermal approach for the high-yield synthesis of cube-like Pt nanoassemblies （Pt-CNAs） with porous cavities and rough surfaces based on the self-assembly of zero dimensional Pt nanocrystals. In this process, arginine acts as the reductant, structure directing agent, and linker between adjacent nanocrystals. Interestingly, the Pt-CNAs exhibit single-crystal structures with dominant {100} facets, as evidenced by X-ray diffraction. Based on electrocatalytic studies, the as-synthesized Pt-CNAs exhibit improved electrocatalytic activity as well as good stability and CO tolerance in the methanol oxidation reaction. The Pt-CNA＇s good performance is attributed to their unique morphology and surface structure. We believe that the synthetic strategy outlined here could be extended to other rationally designed monometallic or bimetallic nanoassemblies for use in high performance fuel cells.展开更多
基金financially supported by the Liaoning Revitalization Talents Program (No.XLYC2403107)the Excellent Youth Science Foundation of Liaoning Province (No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education (No.LJ212410163015)。
文摘Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.
基金supported by the National Natural Science Foundation of China,(Nos.82272151,82204318)Liaoning Revitalization Talents Program(No.XLYC2203083)+2 种基金Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220389)Postdoctoral Fellowship Program of CPSF(No.GZC20231732)China Postdoctoral Science Foundation(Nos.2023TQ0222,2023MD744229).
文摘Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy,mainly comprise drug modules,response modules and modification modules.However,existing studies usually compare the differences between single types of modification modules,neglecting the impact of steric-hindrance effect caused by chemical structure.Herein,single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs(P-LA_(C18)and P-BAC18),and the in-depth insights of the sterichindrance effect on prodrug nanoassemblies were explored.Notably,the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance.Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents,showing faster drug release and stronger antitumor efficacy,but with poorer safety.In contrast,two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics,tumor accumulation and safety due to the good size stability,thus ensuring equivalent antitumor efficacy at tolerance dose.These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structureactivity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.
基金supported by National Natural Science Foundation of China(No.82161138029)Liaoning Revitalization Talents Program(No.XLYC2402040)the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007).
文摘Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.
文摘Successful chemotherapy with paclitaxel(PTX)is impeded by multidrug resistance(MDR)in tumor cells.In this study,lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel(BOR/PTX LANs)were prepared to circumvent MDR in C6 glioma cells.The physiochemical properties including particle size,encapsulation efficiency and morphology were evaluated in vitro.Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells.The cytotoxicity of the BOR/PTX LANs was determined by MTT assay.After that,the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis.BOR/PTX LANs have a higher entrapment efficiency(90.4±1.2%),small particle size(107.5±3.2 nm),narrow distribution(P.I.=0.171±0.02).The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipidalbumin nanoassemblies(PTX LANs)in quantitative research.The result was further confirmed by confocal laser scanning microscopy qualitatively.The cellular uptake was energy-,timeand concentration-dependent,and clathrin-and endosome/lysosome-associated pathways were involved.The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol.Moreover,the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues,demonstrating the tumor targeted ability of BOR/PTX LANs.These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition,and shown the potential for treatment of gliomas.
基金supported by the National Nature Science Foundation of China(No.81803029)the Science and Technology Foundation of Yuzhong District,Chongqing(No.20210179)the Nature Science Foundation of Chongqing(No.cstc2021jcyjmsxmX1089)。
文摘Chemotherapy has been recommended as the standard protocol for triple-negative breast cancer(TNBC)at the advanced stage.However,the current treatment is unsatisfactory due to inefficient drug accumulation and rapid chemo-resistance.Thus,rational design of advanced drug delivery systems that can induce multiple cell death pathways is a promising strategy to combat TNBC.Ferroptosis is a powerful non-apoptotic cell death modality,showing potential in tumor inhibition.Herein,we propose a binary prodrug nanoassemblies that combines chemotherapy with ferroptosis for TNBC treatment.In this system,paclitaxel is linked with paracetamol(ferroptosis activator)by a disulfide linkage to construct self-assembly prodrug.Meanwhile,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-methyl(polyethylene glycol)-2000-tyrosine(DSPE-PEG2k-tyrosine)is applied for large neutral amino acid transporter 1(LAT1)targeting,which is highly expressed in TNBC.The prodrug nanoassemblies exhibit good stability and a glutathione(GSH)-responsive release profile.Furthermore,the LAT1-targeted nanoassemblies show stronger cytotoxicity,higher cellular uptake,and more obvious ferroptosis activation than non-decorated ones.In a TNBC mice model,the prodrug nanoassemblies demonstrate strong anti-tumor efficacy.The application of ferroptosis-assisting chemotherapy may provide a promising strategy for TNBC therapy.
基金supported by the National Natural Science Foundation of China (grant numbers:81974498)Natural Science Foundation of Shandong Province (grant numbers:ZR2019BH079)。
文摘Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-ofconcept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation,we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug interaction.Furthermore, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.
基金supported by the National Natural Science Foundation of China (No. 21805245)the Zhejiang Public Welfare Technology Application Research Project (LGG19B050001)the National Students’ Innovation and Entrepreneurship Training Program of Zhejiang Normal University (201910345032, Z.J. Wang)。
文摘As a representative type of self-supported templates, cyano-bridged cyanogels provide ideal plateaus for synthesis of three-dimensional(3 D) nanostructures. Herein, 3 D pomegranate-like Fe-doped NiCo nanoassemblies(3 D PG-NiCoFe NAs) were synthesized via facile one-step bi-component cyanogel reduction with NaBH_4 as the reducing agent. Specifically, the influence of the incorporated Fe amount was carefully investigated by finely adjusting the feeding molar ratios of the Ni/Co/Fe atoms in the precursors.By virtue of the unique structure and enriched oxygen vacancies originated from well-modulated electronic structures, the 3 D PG-NiCoFe-211 NAs exhibited outstanding electrocatalytic performances for oxygen evolution reaction(OER) in alkaline solution, outperforming commercial RuO_2 catalyst. The current incorporation of foreign metal atom into host material provides some valuable insights into design and synthesis of metal-based nanocatalysts for constructing practical water splitting devices.
基金supported in part by grants from the National Natural Science Foundation of China (No. 21871108)the Program for Innovative Teams of Outstanding Young and Middle-Aged Researchers in the Higher Education Institutions of Hubei Province(No. T201702)。
文摘In this paper, cucurbit[7]uril(CB[7])-mediated three-dimensional gold nanoassemblies were successfully prepared to increase the loaded amount of CB[7] and enhance the electrochemical detection of amino acids. Particle sizes of gold nanoparticles(Au NPs) significantly affect stability and detection sensitivity of nanoassemblies. The volume of gold nanoassemblies first increased and then decreased with the increase of CB[7] concentration. The 3D gold nanoassemblies composed of 16 nm Au NPs and 100 μmol/L CB[7]had excellent stability and maximum volume, exhibiting more sensitive detection for a variety of amino acids. And the detection limits of aromatic amino acids are lower in virtue of the higher binding constant between aromatic amino acids and CB[7]. This study will develop and deepen our understanding of molecular recognition in amino acids detection.
基金financially supported by the National Natural Science Foundation of China(No.82204317)the Liaoning Revitalization Talents Program(No.XLYC2403107)+1 种基金the Excellent Youth Science Foundation of Liaoning Province(No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education(No.LJ212410163015).
文摘Oxaliplatin(OXA)has shown excellent potential in inducing immunogenic cell death and enhancing immunotherapy.However,the poor physicochemical properties of oxaliplatin make it difficult to achieve efficient synchronous delivery and synergistic immunotherapy with immune checkpoint inhibitors.To address this,we designed structurally optimized dual-wing butterfly prodrugs:oxaliplatin prodrug(POP)that enhances immunogenicity and reducible NLG919 homodimer(NSSN)that mitigates immunosuppression.Structural optimization of dual-wing butterfly prodrugs significantly enhanced lipid solubility compared to the parent drugs.It is worth noting that we assembled two dual-wing butterfly prodrugs,POP and NSSN,together into hybrid nanoassemblies(NAs),achieving advantages such as stable assembly,flexible dosing,and collaborative therapy.Dual-wing butterfly prodrug-driven hybrid NAs demonstrated enhanced antitumor efficacy and metastasis control in experimental models,with biocompatibility confirmed through biosafety evaluations.This work proposes a co-delivery strategy based on dual-wing butterfly prodrugs as a clinically translatable candidate.
基金gotapproval from the Institutional Animal Ethical Care Committee(IAEC)of Shenyang Pharmaceutical University(ethical code:SYPU-IACUC-2022-0302-010).
文摘The clinical utility of irinotecan is restricted by individual variability in carboxylesterase expression.Direct administration of its active metabolite,7-ethyl-10-hydroxycamptothecin(SN38),presents an appealing alternative due to its potent anti-tumor efficacy.However,the undesirable properties of SN38,such as poor water solubility and nontarget toxicity,present significant hurdles to its clinical development.Prodrug nanoassemblies based on modular design strategy show promise in overcoming these challenges by enhancing drug delivery and selective activation.In modular design,the modification module plays a crucial role in improving the self-assembly capability of prodrugs.While current studies mainly focus on using straight aliphatic chains for prodrug design,branched aliphatic chains emerge as superior alternatives warranting further investigation.In this study,we selected 2-heptylundecanol(BAlc18)as modification module to construct an SN38 prodrug.Through exquisite design,SN38-SS-BAlc18 NPs integrated prominent properties in selfassembly capability,specific activation and biocompatibility,resolving the challenges of irinotecan and SN38,ultimately demonstrating excellent anti-tumor efficacy.This exploration enriched the design theory of prodrug nanoassemblies that can effectively balance safety and colorectal anti-tumor efficacy.
基金supported by the National Key R&D Program of China(2022YFE0111600)the Key Research and Development Program of Liaoning Province(2024JH2/102500061)+7 种基金the Youth Innovation Team of Liaoning Provincial Department of Education(LJ222410163049)the Liaoning Revitalization Talents Program(XLYC2203083)the Open Fund of High-level Key Discipline of Chemistry of Chinese Medicine of the State Administration of Traditional Chinese Medicinethe Anhui University of Chinese Medicine(HKDCCM2024007)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(CPSF)(GZC20231-732)the China Postdoctoral Science Foundation(2023TQ0222,2023MD744229)the General Program of Department of Education of Liaoning Province(JYTMS20231372)the Doctoral Scientific Research Staring Foundation of Liaoning Province(2024-BS-073)。
文摘Irinotecan,one of the most effective chemotherapeutic agents for the treatment of advanced colorectal cancer,suffers from extremely low activatability and non-selective tumor activation.7-Ethyl-10-hydroxy-camptothecin(SN38),the active metabolite of irinotecan,has been limited in clinical development due to poor water solubility and stability.Here,the thioether bond and disulfide bond were employed as response modules to construct tumor-selective SN38 prodrug nanoassemblies(SN38-S-C_(21) NPs and SN38-SS-C_(21) NPs).11-Henicosanol was chosen as a self-assembly module to enhance stability.Both SN38-S-C_(21) NPs and SN38-SS-C_(21) NPs presented ultra-high in vivo stability with a 12146-fold and 23151-fold elevation in the area under the curve(AUC)compared to SN38.Moreover,SN38-S-C_(21) NPs and SN38-SS-C_(21) NPs showed a significant reduction of SN38exposure in blood compared to irinotecan.Importantly,the prodrug nanoassemblies enabled selective activation within tumor cells,and the conversion rates of SN38-SS-C_(21) NPs and SN38-S-C_(21) NPs to SN38 were 10-and 7-fold higher than irinotecan.Compared with SN38-S-C_(21) NPs,the superior in vivo stability,SN38 conversion efficiency and tumor selectivity of SN38-SSC_(21) NPs resulted in potent antitumor effects and safety.Our findings proved that the disulfide bond was more suitable for constructing high-performance SN38 prodrug nanoassemblies,which showed significant promise for the rational design of SN38 nanomedicines.
基金support from the Key research and development program of Liaoning Province(No.2024JH2/102500061)Youth innovation team of Liaoning Province Department of Education(No.LJ222410163049)Liaoning Revitalization Talents Program(No.XLYC2203083).
文摘Prodrug-based nanoassemblies have emerged as advanced carrier-free nanomedicines.These prodrugs typically consist of drug modules,response modules,and modification modules.The general role of modification modules is to modulate the self-assembly ability of the prodrugs.How to optimize the structure of modification modules for balanced efficacy and safety of high-toxicity chemotherapeutic drugs deserves to be further investigated.In this study,a modification strategy of aliphatic alcohols with various chain lengths(SC_(4),SC_(8),SC_(12),SC_(16) and SC_(20))was carried out to design five cabazitaxel(CBZ)prodrugs.Among them,CBZ-SC NPs with shorter chain length(SC_(4) and SC_(8))showed poor self-assembly stability.CBZ-SC_(12) NPs also failed to remain stable while the other two CBZ-SC NPs exhibited good stability.In turn,the drug release rate was hindered by the increasing chain length.CBZ-SC_(12) NPs caused kidney damage due to their high redox-sensitivity and rapid release rate during circulation.By contrast,CBZ-SC NPs with longer chain length(SC_(16) and SC_(20))not only demonstrated superior stability with improved pharmacokinetic behavior,but also might solve the dilemma of dose-related toxicity caused by CBZ.Overall,these findings emphasized the importance of chain length in modification module to modulate the efficacy and safety of CBZ prodrug nanoassemblies.
基金the National Key R&D Program of China(No.2022YFE0111600)the National Natural Science Foundation of China(No.82204318)+2 种基金Key research and development program of Liaoning Province(No.2024JH2/102500061)Youth innovation team of Liaoning Province Department of Education(No.LJ222410163049)Liaoning Revitalization Talents Program(No.XLYC2203083).
文摘Dimeric prodrug nanoassemblies(DPNAs)offer great potential in improving the efficacy of chemotherapy.Previously,we developed tetrasulfide bonds as a novel response module and the obtainedγ-4S-2CTX NPs demonstrated superlative self-assembly stability and enhanced anti-tumor efficacy.However,current DPNAs mainly rely on simple PEGylation for surface modification to improve blood circulation,which lacks tumor-selective functionality and limits their further application.To address these limitations,we introduced a new surface modification strategy using RM-1 tumor cell membranes(CMs)to enhance biofunctionality.The initial attempt to use CMs as a single surface modification failed because the affinity of nanocores-CMs remains a problem,which affected the stability of membrane-coated DPNAs.To address this,we used 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-2000](DSPE-PEG2k)as an adhesive bridge to improve the affinity between CMs and DPNAs,resulting in a dual-modified formulation termed CM-pDPNAs.This dual modification strategy enhanced CMs binding to DPNAs,enabling precise tumor recognition and internalization,thereby improving tumor elimination efficacy.Furthermore,this approach addressed key challenges associated with current CM-coated nanoparticles(CM-NPs),including complex preparation procedures and poor drug-carrier compatibility.This work elucidates the application of CMs as surface modification modules,paving the way for the next generation of biomimetic prodrug nanoassemblies with superior stability and tumor specficity.
文摘Fengxiang Liu1,,Rongzheng Liu1,,Xiaoyuan Fan2,,Xia Wang2,,Kaiyuan Wang1,,Hainan Zhao3,,Hao Ye4,Shunzhe Zheng1,Xiao Kuang1,Yinxian Yang1,Haotian Zhang5,Qiming Kan5,Zhonggui He1,6,Jian Chen 7,and Jin Sun1,61 Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China 2 School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China 3 Nephrology department,The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China 4 Multi-Scale Robotics Lab(MSRL),Institute of Robotics&Intelligent Systems(IRIS),ETH Zurich 8092,Switzerland 5 School of Life Science and Biopharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China 6 Joint International Research Laboratory of Intelligent Drug Delivery Systems,Ministry of Education,Shenyang 110016,China 7 School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China§Fengxiang Liu,Rongzheng Liu,Xiaoyuan Fan,Xia Wang,Kaiyuan Wang,and Hainan Zhao contributed equally to this work.
文摘In the originally published version of this article,the authors identified inadvertent errors in the preparation of Fig.7A and B.During assembly of the figure,incorrect images from the same batch of raw data were mistakenly selected and duplicated across two separate studies.The figure has now been replaced with the correct images sourced from the same original dataset.
基金supported by Liaoning BaiQianWan Talents Program(No.2016921064,China)Nature Science Foundation of Guangdong Province(No.2016A020217017,China)
文摘Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reactive oxygen species(ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid(LA) and docetaxel(DTX). This mono thioether-linked conjugates(DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve(AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4 T1 xenograft. It turned out this nanoassemblies couldenhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.
基金This research was sponsored by National Natural Sdence Foundation of China （Nos. 21473111, 21576139, 21503111, 21376122, and 21273116）, United Fund of NSFC and Yunnan Province （No. Ul137602）, Natural Science Foundation of Jiangsu Province （No. BK20131395）, Natural Science Foundation of Shaanxi Province （No. 2015JM2043）, Fundamental Research Funds for the Central Universities （No. GK201402016）, China Scholarship Council （CSC, No. 201506860013）, University Postgraduate Research and Innovation Project in Jiangsu Province （No. KYZZ15_0213）, National and Local Joint Engineering Research Center of Biomedical Functional Material, and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The authors also thank John B. Goodenough UT-Austin for his help with XPS and electrochemical measurements during the article revision.
文摘Novel self-assembled architectures have received a growing amount of attention and have significant potential for application in catalysis/electrocatalysis. Herein, we take advantage of the unique coordination and self-assembly properties of arginine for the preparation of dendritic PtCu bimetallic nanoassemblies with tunable chemical composition and structure. Strong interactions between the arginine molecules are key in driving the self-assembly of primary nanocrystals. In addition, the strong coordination interactions between arginine and metal ions is responsible for the formation of Pt-Cu alloys. We also investigated the electrocatalytic activity of various dendritic PtCu bimetallic nanoassemblies towards the methanol oxidation reaction. PtBCUl nanoassemblies exhibited excellent electrocatalytic activity and stability in comparison with other PtCu bimetallic nanoassemblies （PtlCu3, PtlCu~） and commercial Pt black, due to their unique dendritic structures and the synergistic effect between the Pt and Cu atoms.
基金supported by grants from the National Natural Science Foundation of China(grant no.81773669,82073788)National Major Science and Technology Projects of China(grant no.2017YFA0205400).
文摘Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis;however,the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells.Here,we report reactive oxygen species(ROS)-responsive and size-reducible nanoassemblies,formed by multivalent host-vip interactions betweenβ-cyclodextrins(β-CD)-anchored discoidal recombinant high-density lipoprotein(NP^(3)_(ST))and hyaluronic acid-ferrocene(HA-Fc)conjugates.The HA-Fc/NP^(3)_(ST)nanoassemblies have extended blood circulation time,specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium,rapidly disassemble in response to excess ROS in the intimal and release smaller NP^(3)_(ST),allowing for further plaque penetration,macrophage-targeted cholesterol efflux and drug delivery.In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP^(3)_(ST)reduces plaque size by 53%,plaque lipid deposition by 63%,plaque macrophage content by 62%and local inflammatory factor level by 64%compared to the saline group.Meanwhile,HA-Fc/NP^(3)_(ST)alleviates systemic inflammation characterized by reduced serum inflammatory factor levels.Collectively,HA-Fc/NP^(3)_(ST)nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability,thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
基金We are grateful for financial support from the US National Science Foundation （NSF） （CAREER program and No. DMR-0706431）, US Department of Defense （DoD） （No. W911NF-09-1-0236）, the Alfred P. Sloan Scholarship, the Camille Dreyfus Teacher-Scholar Award, DoD-Army Research Office （ARO）, and the W. M. Keck Foundation. We are also indebted to Dr. Udai Singh for assistance with flow cytometry and Laying Wu for TEM and SEM analyses.
文摘Poly（caprolactone-b-2-vinylpyridine） （PCL-P2VP） coated with folate-conjugated M13 （FA-M13） provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin （DOX）. The DOXqoaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.
文摘Controllable self-assembly of noble metal nanocrystals is of broad interest for the development of highly active electrocatalysts. Here we report an efficient arginine-mediated hydrothermal approach for the high-yield synthesis of cube-like Pt nanoassemblies （Pt-CNAs） with porous cavities and rough surfaces based on the self-assembly of zero dimensional Pt nanocrystals. In this process, arginine acts as the reductant, structure directing agent, and linker between adjacent nanocrystals. Interestingly, the Pt-CNAs exhibit single-crystal structures with dominant {100} facets, as evidenced by X-ray diffraction. Based on electrocatalytic studies, the as-synthesized Pt-CNAs exhibit improved electrocatalytic activity as well as good stability and CO tolerance in the methanol oxidation reaction. The Pt-CNA＇s good performance is attributed to their unique morphology and surface structure. We believe that the synthetic strategy outlined here could be extended to other rationally designed monometallic or bimetallic nanoassemblies for use in high performance fuel cells.
