Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer(TNBC)therapy.Ho...Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer(TNBC)therapy.However,the ferroptosis accompanied with down-regulation of glutathione peroxidase 4(GPX4)lead to CD36-mediated tumor-infiltrating CD8^(+)T cells uptaking fatty acids,resulting in the negative action on immunotherapeutic efficacy.Herein,the albumin nanoparticles,abbreviated as LHS NPs,were designed by co-assembly of hemin,linoleic acid-cystamine,and a CD36 inhibitor sulfosuccinimide oleate,to bi-directionally manipulated ferroptosis in tumor and CD8^(+)T cells for TNBC therapy.LHS NPs exerted more efficient reactive oxygen species generation,glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes,which amplified the positive action on ferroptosis in tumor cells.Meanwhile,LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8^(+)T cells,thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death,proliferation of CD4+CD8^(+)T cells and natural killer cells,alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells,and repolarization of the M2-to M1-phenotype tumor-associated macrophages.Thus,LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lungmetastasis of 4T1-tumormice.Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8^(+)T cells on TNBC chemoimmunotherapy.展开更多
Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery.However,prodrug activation remains a rate-limiting step for exer...Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery.However,prodrug activation remains a rate-limiting step for exerting therapeutic actions,which requires to quickly reach the minimum valid concentrations of free drugs.Fortunately,we find that a natural compound(BL-193)selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin(PPT)at ineffective dose concentrations.Based on this,we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT.Specifically,a redox-sensitive prodrug(PSSF)of PPT is synthesized by coupling 9-fluorenyl-methanol(Fmoc-OH)with PPT linked via disulfide bond.Intriguingly,PSSF with aπ-conjugated structure readily co-assembles with BL-193 into stable nanoassembly.Significantly,BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic windowfor PPT.Moreover,prodrug design and precise hybrid nanoassembly well manage off-target toxicity.As expected,such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses.This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.展开更多
Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evi...Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.展开更多
Monodisperse nanoparticle assembly with tunable structure, composition and properties can be taken as a superstructured building block for the construction of hierarchical nanostruc tures from the bottom up, which als...Monodisperse nanoparticle assembly with tunable structure, composition and properties can be taken as a superstructured building block for the construction of hierarchical nanostruc tures from the bottom up, which also represents a great challenge in nanotechnology. Here we report on a facile and controllable method that enables a high yield fabricatioa of uniform gold nanoparticle （AuNP） coresatellites with definable number （in average） of the satellite particles and tunable coretosatellite distance. The formation of the coresatellite nanostruc tures is driven by programmable DNAbasepairing, with the resulting nanocomplexes being isolatable via gel electrophoresis. By rationally controlling the DNA coverages on the core and shell particles, high production yields are achieved for the assembly/isolation process. As well, benefiting from a minimum DNA coverage on the satellite AuNPs, a strong affinity is observed for the asprepared coresatellites to get adsorbed on proteincoated graphene ox ide, which allows for a twodimensional hierarchical assembly of the coresatellite structures. The resulting hierarchical nanoassemblies are expected to find applications in various areas, including plasmonics, biosensing, and nanocatalysis. The method should be generalizable to make even more complicated and higherorder structures by making use of the structural programmability of DNA molecules.展开更多
Here,a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide(BPO) based on its deboronation.This gold nanoassembly(the BE-Au NPs_(12/65)) wa s constructed via borate es...Here,a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide(BPO) based on its deboronation.This gold nanoassembly(the BE-Au NPs_(12/65)) wa s constructed via borate ester formation between large 4-mercaptophenylboronic acid(MPBA) modified Au NPs(the MPBAAu NPs_(65),as cores) and small dopamine modified AuNPs(the D PA-AuNPs_(12),as satellites).Particularly,upon addition of BPO,it would trigger the deboronation for the BE-AuNPs_(12/65) probes accompanying with distinct color changes from blue,purple to wine red,which implied the disassembly of the core/satellite nanostructure after the breakage of carbon to boron chemical bond.By measuring the absorbance ratio at 665 nm and 545 nm,quantification of BPO was achieved in the range of 10.0-100.0 nmol/L,which could also be easily observed by naked eyes.The nanoprobe utilized a boronate deprotection mechanism and the LSPR properties of Au NPs to provide high selectivity for detecting BPO over similar ROS/RNS with the limit of detection as low as 7.2 nmol/L.The practical applicability of this assay was verified through successful determining BPO in flour samples,which demonstrated its great potentials in food safety field.展开更多
Drug resistance is a major obstacle in tumor therapy.One effective approach to overcoming this issue is by improving the penetration of drugs into the lesions.Here,we report size shrinkable dendrimer-lipid hybrid nano...Drug resistance is a major obstacle in tumor therapy.One effective approach to overcoming this issue is by improving the penetration of drugs into the lesions.Here,we report size shrinkable dendrimer-lipid hybrid nanoassemblies(PATU-lipid-PEG/DOX).The PATU-lipid-PEG/DOX have initial sizes of~92 nm,which are ideal for blood circulation and tumor vascular penetration.Once PATU-lipid-PEG/DOX at tumor sites,they will disassemble and release small dendrimers(~3 nm)to realize deep tumor penetration.As a result,Doxorubicin(DOX)can be delivered intracellularly,thereby reversing tumor multidrug resistance.The efficacy of PATU-lipidPEG/DOX was validated in drug-resistant tumor mice.This study provides a versatile drug delivery platform to address the challenges of tumor drug resistance.展开更多
RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and p...RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging.Recently,more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating.Due to the flexibility and deformability of nucleic acids,the nanoassemblies could be fabricated with different shapes and structures.With hybridization,nucleic acid nanoassemblies,including DNA and RNA nanostructures,can be applied to enhance RNA therapeutics and diagnosis.This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.展开更多
Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a c...Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect.In this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into mB4S.After internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP secretion.Meanwhile,diABZI effectively activated the STING pathway.Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.展开更多
Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolv...Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.展开更多
Phototherapy has been intensively investigated as a non-invasive cancer treatment option.However,its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity.To achieve hig...Phototherapy has been intensively investigated as a non-invasive cancer treatment option.However,its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity.To achieve high therapeutic efficiency and high security,a nanoassembly of Forster Resonance Energy Transfer(FRET)photosensitizer pairs is developed on basis of dual-mode photosensitizer co-loading and photocaging strategy.For proof-of-concept,an erythrocyte-camouflaged FRET pair co-assembly of chlorine e6(Ce6,FRET donor)and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide(DiR,FRET acceptor)is investigated for breast cancer treatment.Notably,Ce6 in the nanoassemby is quenched by DiR and could be unlocked for photodynamic therapy(PDT)only when DiR is photobleached by 808-nm laser.As a result,Ce6-caused phototoxicity could be well controlled.Under cascaded laser irradiation(808-660 nm),tumor-localizing temperature rise following laser irradiation on DiR not only induces tumor cell apoptosis but also facilitates the tumor penetration of NPs,relieves tumor hypoxia,and promotes the PDT efficacy of Ce6.Such FRET pair-based nanoassembly provides a new strategy for developing multimodal phototherapy nanomedicines with high efficiency and good security.展开更多
Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy.Herein,a pH-responsive gold nanoassembly is designed to overcome these problems.Polyethylene glycol linked raltitrexed(RT...Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy.Herein,a pH-responsive gold nanoassembly is designed to overcome these problems.Polyethylene glycol linked raltitrexed(RTX,target ligand and chemotherapy drug)and two tertiary amine molecules(1-(2-aminoethyl)pyrrolidine and N,N-dibutylethylenediamine)are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX).The Au-NNP(RTX)nanoassembly could remain at about 160 nm at the blood circulation(pH 7.4),while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH(pH 6.8).This pH-responsive disassembly behavior endows Au-NNP(RTX)better tumor tissue permeability through the better diffusion brought by the size reduction.Meanwhile,after disassembly,more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability.Most importantly,the results show that Au-NNP(RTX)possesses of high tumor accumulation and effective tumor penetration,thereby enhancing the tumor chemo-radiotherapy efficiency.展开更多
In this work, we present plasma etching alone as a directed assembly method to both create the nanodot pattern on an etched polymeric (PMMA) film and transfer it to a silicon substrate for the fabrication of silicon n...In this work, we present plasma etching alone as a directed assembly method to both create the nanodot pattern on an etched polymeric (PMMA) film and transfer it to a silicon substrate for the fabrication of silicon nanopillars or cone-like nanostructuring. By using a shield to control sputtering from inside the plasma reactor, the size and shape of the resulting nanodots can be better controlled by varying plasma parameters as the bias power. The effect of the shield on inhibitor deposition on the etched surfaces was investigated by time-of-flight secondary ion mass spectroscopy (ToF-SIMS) measurements. The fabrication of quasi-ordered PMMA nanodots of a diameter of 25 nm and period of 54 nm is demonstrated. Pattern transfer to the silicon substrate using the same plasma reactor was performed in two ways:(a) a mixed fluorine-fluorocarbon-oxygen nanoscale etch plasma process was employed to fabricate silicon nanopillars with a diameter of 25 nm and an aspect ratio of 5.6, which show the same periodicity as the nanodot pattern, and (b) high etch rate cryogenic plasma process was used for pattern transfer. The result is the nanostructuring of Si by high aspect ratio nanotip or nanocone-like features that show excellent antireflective properties.展开更多
Chemistry gives us the ability to manipulate atoms and molecules into nanometer and micrometer scale building blocks,while the science of crystallography is concerned with the spatial arrangement of atoms,ions,and mol...Chemistry gives us the ability to manipulate atoms and molecules into nanometer and micrometer scale building blocks,while the science of crystallography is concerned with the spatial arrangement of atoms,ions,and molecules and thus the morphology and structures of materials.Complex three-dimensional ZnS nanostructures have been fabricated via step-by-step crystallographically-controlled chemical processes.Tricrystals of ZnS whiskers were prepared via a controlled thermal evaporation process,and then the tricrystals were thermally treated in an atmosphere formed by evaporating B N O precursors into N2/NH3 to afford BN-coated arrays of nanobranches.The ZnS nanobranches grew epitaxially on the ternary facets and extended in three[0001]directions forming ordered nanostructures.Meanwhile,the protecting insulating sheath of BN formed on the ZnS nanostructures confined the growth of the nanospines and enhanced their stability.The method may be extended to fabricate other semiconductor nanomaterials with novel structures.展开更多
Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease(IBD),attributed to their robust biological activity,multi-target effects,and elevated safety profile...Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease(IBD),attributed to their robust biological activity,multi-target effects,and elevated safety profile.Although promising,the clinical application of phytoconstituents have been impeded by poor water solubility,low oral bioavailability,and inadequate colonic targeting.Recent advancements in nanotechnology has offered prospective avenues for the application of phytoconstituents in the treatment of IBD.A common strategy involves encapsulating or conjugating phytoconstituents with nanocarriers to enhance their stability,prolong intestinal retention,and facilitate targeted delivery to colonic inflammatory tissues.Furthermore,drawing inspiration from the self-assembling nanostructures that emerge during the decoction process of Chinese herbs,a variety of natural active compounds-based nanoassemblies have been developed for the treatment of IBD.They exhibit high drug-loading capacities and surmount the challenges posed by poor water solubility and low bioavailability.Notably,phyto-derived nanovesicles,owing to their unique structure and biological functions,can serve as therapeutic agents or novel delivery vehicles for the treatment of IBD.Consequently,this review provides an extensive overview of emerging phytoconstituent-derived nano-medicines/vesicles for the treatment of IBD,intending to offer novel insights for the clinical management of IBD.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
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
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
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
基金supported by the National Nature Science Foundation of China(NO.82260699)the Science and Technology Leading Talents of Ningxia(NO.2022GKLRLX011)the West Light Foundation of The Chinese Academy of Sciences(the Science and Technology Department of Ningxia,Department of Science and Technology Cooperation[2021]NO.2).
文摘Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer(TNBC)therapy.However,the ferroptosis accompanied with down-regulation of glutathione peroxidase 4(GPX4)lead to CD36-mediated tumor-infiltrating CD8^(+)T cells uptaking fatty acids,resulting in the negative action on immunotherapeutic efficacy.Herein,the albumin nanoparticles,abbreviated as LHS NPs,were designed by co-assembly of hemin,linoleic acid-cystamine,and a CD36 inhibitor sulfosuccinimide oleate,to bi-directionally manipulated ferroptosis in tumor and CD8^(+)T cells for TNBC therapy.LHS NPs exerted more efficient reactive oxygen species generation,glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes,which amplified the positive action on ferroptosis in tumor cells.Meanwhile,LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8^(+)T cells,thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death,proliferation of CD4+CD8^(+)T cells and natural killer cells,alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells,and repolarization of the M2-to M1-phenotype tumor-associated macrophages.Thus,LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lungmetastasis of 4T1-tumormice.Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8^(+)T cells on TNBC chemoimmunotherapy.
基金supported by the Basic Research Projects of Liaoning Provincial Department of Education(LJKZZ20220109)the Shenyang Youth Science and Technology Innovation Talents Program(No.RC210452)+1 种基金the National Natural Science Foundation of China(No.82204317)the Natural Science Foundation of Liaoning Province(No.2022-BS-162).
文摘Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery.However,prodrug activation remains a rate-limiting step for exerting therapeutic actions,which requires to quickly reach the minimum valid concentrations of free drugs.Fortunately,we find that a natural compound(BL-193)selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin(PPT)at ineffective dose concentrations.Based on this,we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT.Specifically,a redox-sensitive prodrug(PSSF)of PPT is synthesized by coupling 9-fluorenyl-methanol(Fmoc-OH)with PPT linked via disulfide bond.Intriguingly,PSSF with aπ-conjugated structure readily co-assembles with BL-193 into stable nanoassembly.Significantly,BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic windowfor PPT.Moreover,prodrug design and precise hybrid nanoassembly well manage off-target toxicity.As expected,such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses.This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.
基金financially supported by the Liaoning Revitalization Talents Program (No. XLYC1907129)the Excellent Youth Science Foundation of Liaoning Province (No. 2020-YQ-06)the China Postdoctoral Science Foundation (No. 2020M670794)。
文摘Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.
文摘Monodisperse nanoparticle assembly with tunable structure, composition and properties can be taken as a superstructured building block for the construction of hierarchical nanostruc tures from the bottom up, which also represents a great challenge in nanotechnology. Here we report on a facile and controllable method that enables a high yield fabricatioa of uniform gold nanoparticle （AuNP） coresatellites with definable number （in average） of the satellite particles and tunable coretosatellite distance. The formation of the coresatellite nanostruc tures is driven by programmable DNAbasepairing, with the resulting nanocomplexes being isolatable via gel electrophoresis. By rationally controlling the DNA coverages on the core and shell particles, high production yields are achieved for the assembly/isolation process. As well, benefiting from a minimum DNA coverage on the satellite AuNPs, a strong affinity is observed for the asprepared coresatellites to get adsorbed on proteincoated graphene ox ide, which allows for a twodimensional hierarchical assembly of the coresatellite structures. The resulting hierarchical nanoassemblies are expected to find applications in various areas, including plasmonics, biosensing, and nanocatalysis. The method should be generalizable to make even more complicated and higherorder structures by making use of the structural programmability of DNA molecules.
基金financial support from the National Natural Science Foundation of China(Nos.U1736201,21677019 and 41403021)Capital Health Research and Development of Special(No.2018-4-1014)the Key Research and Development Program of Beijing(No.D171100008317001)。
文摘Here,a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide(BPO) based on its deboronation.This gold nanoassembly(the BE-Au NPs_(12/65)) wa s constructed via borate ester formation between large 4-mercaptophenylboronic acid(MPBA) modified Au NPs(the MPBAAu NPs_(65),as cores) and small dopamine modified AuNPs(the D PA-AuNPs_(12),as satellites).Particularly,upon addition of BPO,it would trigger the deboronation for the BE-AuNPs_(12/65) probes accompanying with distinct color changes from blue,purple to wine red,which implied the disassembly of the core/satellite nanostructure after the breakage of carbon to boron chemical bond.By measuring the absorbance ratio at 665 nm and 545 nm,quantification of BPO was achieved in the range of 10.0-100.0 nmol/L,which could also be easily observed by naked eyes.The nanoprobe utilized a boronate deprotection mechanism and the LSPR properties of Au NPs to provide high selectivity for detecting BPO over similar ROS/RNS with the limit of detection as low as 7.2 nmol/L.The practical applicability of this assay was verified through successful determining BPO in flour samples,which demonstrated its great potentials in food safety field.
基金financially supported by the National Natural Science Foundation of China(No.22075247)the Zhejiang Provincial Natural Science Foundation of China(No.LGF21C100001)+2 种基金the China Postdoctoral Science Foundation(No.2023M743104)the Postdoctoral Fellowship Program of CPSF(No.GZC20232365)support by Zhejiang Provincial Key Laboratory of TCM for Innovative R&D and Digital Intelligent Manufacturing of TCM Great Health Products。
文摘Drug resistance is a major obstacle in tumor therapy.One effective approach to overcoming this issue is by improving the penetration of drugs into the lesions.Here,we report size shrinkable dendrimer-lipid hybrid nanoassemblies(PATU-lipid-PEG/DOX).The PATU-lipid-PEG/DOX have initial sizes of~92 nm,which are ideal for blood circulation and tumor vascular penetration.Once PATU-lipid-PEG/DOX at tumor sites,they will disassemble and release small dendrimers(~3 nm)to realize deep tumor penetration.As a result,Doxorubicin(DOX)can be delivered intracellularly,thereby reversing tumor multidrug resistance.The efficacy of PATU-lipidPEG/DOX was validated in drug-resistant tumor mice.This study provides a versatile drug delivery platform to address the challenges of tumor drug resistance.
基金supported by the National Science Foundation of China(No.82003689,to Mengnan Zhao,China)the Outstanding Young Scientific Talent Foundation of Sichuan Province(No.2022JDJQ0052,to Sanjun Shi,China)+3 种基金the China Postdoctoral Science Foundation(No.2021M690489,to Mengnan Zhao,China)the Project of High-Level Talents in Sichuan Province(No.003113014003,to Sanjun Shi,China)the International Postdoctoral Exchange Fellowship Program(No.YJ20200040,to Mengnan Zhao,China)the Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine(No.BSH2020006,to Mengnan Zhao,China).
文摘RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging.Recently,more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating.Due to the flexibility and deformability of nucleic acids,the nanoassemblies could be fabricated with different shapes and structures.With hybridization,nucleic acid nanoassemblies,including DNA and RNA nanostructures,can be applied to enhance RNA therapeutics and diagnosis.This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.
基金This work was supported by National Natural Science Foundation of China(32271445,52073193,and 82202322)National Science and Technology Major Project of China(2023YFB3810004)+2 种基金1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21013,China)the Sichuan Science and Technology Program(2023NSFSC1592,China),the China Postdoctoral Science Foundation(2021M692255,China)the Post-Doctor Research Project,West China Hospital,Sichuan University(2020HXBH094,China).
文摘Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect.In this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into mB4S.After internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP secretion.Meanwhile,diABZI effectively activated the STING pathway.Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.
基金supported by Science and Technology Major Project of Liaoning(No.2019JH1/10300004,China)the National Natural Science Foundation of China(No.81773656 and 81703451)+2 种基金the Excellent Youth Science Foundation of Liaoning Province(No.2020-YQ-06,China)the China Postdoctoral Science Foundation(No.2020M670794)the Liaoning Revitalization Talents Program(No.XLYC1907129 and XLYC1808017,China)。
文摘Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.
基金supported by the National Natural Science Foundation of China(No.81773656 and 81703451)the Excellent Youth Science Foundation of Liaoning Province(No.2020-YQ-06)+2 种基金the China Postdoctoral Science Foundation(No.2020M670794)the Liaoning Revitalization Talents Program(No.XLYC1907129 and XLYC1808017),Science and Technology Major Project of Liaoning(No.2019JH1/10300004)the National College Students’innovation and entrepreneurship training program(No.201910163200).
文摘Phototherapy has been intensively investigated as a non-invasive cancer treatment option.However,its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity.To achieve high therapeutic efficiency and high security,a nanoassembly of Forster Resonance Energy Transfer(FRET)photosensitizer pairs is developed on basis of dual-mode photosensitizer co-loading and photocaging strategy.For proof-of-concept,an erythrocyte-camouflaged FRET pair co-assembly of chlorine e6(Ce6,FRET donor)and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide(DiR,FRET acceptor)is investigated for breast cancer treatment.Notably,Ce6 in the nanoassemby is quenched by DiR and could be unlocked for photodynamic therapy(PDT)only when DiR is photobleached by 808-nm laser.As a result,Ce6-caused phototoxicity could be well controlled.Under cascaded laser irradiation(808-660 nm),tumor-localizing temperature rise following laser irradiation on DiR not only induces tumor cell apoptosis but also facilitates the tumor penetration of NPs,relieves tumor hypoxia,and promotes the PDT efficacy of Ce6.Such FRET pair-based nanoassembly provides a new strategy for developing multimodal phototherapy nanomedicines with high efficiency and good security.
基金This study is dedicated to 100th anniversary of Chemistry at Nankai University.This work was supported by the National Natural Science Foundation of China(Grant 52073147,51773096,51433004,32071342)Specific Program for High-Tech Leader&Team of Tianjin Government,Tianjin innovation and Promotion Plan Key Innovation Team of Immunoreactive Biomaterials.We appreciate Prof.Qiang Wu at Nankai University for help with the characterization of materials and Dr.Ding Yuxun for help with characterization of penetration.
文摘Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy.Herein,a pH-responsive gold nanoassembly is designed to overcome these problems.Polyethylene glycol linked raltitrexed(RTX,target ligand and chemotherapy drug)and two tertiary amine molecules(1-(2-aminoethyl)pyrrolidine and N,N-dibutylethylenediamine)are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX).The Au-NNP(RTX)nanoassembly could remain at about 160 nm at the blood circulation(pH 7.4),while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH(pH 6.8).This pH-responsive disassembly behavior endows Au-NNP(RTX)better tumor tissue permeability through the better diffusion brought by the size reduction.Meanwhile,after disassembly,more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability.Most importantly,the results show that Au-NNP(RTX)possesses of high tumor accumulation and effective tumor penetration,thereby enhancing the tumor chemo-radiotherapy efficiency.
文摘In this work, we present plasma etching alone as a directed assembly method to both create the nanodot pattern on an etched polymeric (PMMA) film and transfer it to a silicon substrate for the fabrication of silicon nanopillars or cone-like nanostructuring. By using a shield to control sputtering from inside the plasma reactor, the size and shape of the resulting nanodots can be better controlled by varying plasma parameters as the bias power. The effect of the shield on inhibitor deposition on the etched surfaces was investigated by time-of-flight secondary ion mass spectroscopy (ToF-SIMS) measurements. The fabrication of quasi-ordered PMMA nanodots of a diameter of 25 nm and period of 54 nm is demonstrated. Pattern transfer to the silicon substrate using the same plasma reactor was performed in two ways:(a) a mixed fluorine-fluorocarbon-oxygen nanoscale etch plasma process was employed to fabricate silicon nanopillars with a diameter of 25 nm and an aspect ratio of 5.6, which show the same periodicity as the nanodot pattern, and (b) high etch rate cryogenic plasma process was used for pattern transfer. The result is the nanostructuring of Si by high aspect ratio nanotip or nanocone-like features that show excellent antireflective properties.
基金the National Natural Science Foundation of China(20571082,50772125)the Science and Technology Commission of Shanghai(08JC1420700).
文摘Chemistry gives us the ability to manipulate atoms and molecules into nanometer and micrometer scale building blocks,while the science of crystallography is concerned with the spatial arrangement of atoms,ions,and molecules and thus the morphology and structures of materials.Complex three-dimensional ZnS nanostructures have been fabricated via step-by-step crystallographically-controlled chemical processes.Tricrystals of ZnS whiskers were prepared via a controlled thermal evaporation process,and then the tricrystals were thermally treated in an atmosphere formed by evaporating B N O precursors into N2/NH3 to afford BN-coated arrays of nanobranches.The ZnS nanobranches grew epitaxially on the ternary facets and extended in three[0001]directions forming ordered nanostructures.Meanwhile,the protecting insulating sheath of BN formed on the ZnS nanostructures confined the growth of the nanospines and enhanced their stability.The method may be extended to fabricate other semiconductor nanomaterials with novel structures.
基金supported by the National Natural Science Foundation of China(Nos.82273824,31670359 and 82372111)the Liao Ning Revitalization Talents Program(No.XLYC 1905019)。
文摘Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease(IBD),attributed to their robust biological activity,multi-target effects,and elevated safety profile.Although promising,the clinical application of phytoconstituents have been impeded by poor water solubility,low oral bioavailability,and inadequate colonic targeting.Recent advancements in nanotechnology has offered prospective avenues for the application of phytoconstituents in the treatment of IBD.A common strategy involves encapsulating or conjugating phytoconstituents with nanocarriers to enhance their stability,prolong intestinal retention,and facilitate targeted delivery to colonic inflammatory tissues.Furthermore,drawing inspiration from the self-assembling nanostructures that emerge during the decoction process of Chinese herbs,a variety of natural active compounds-based nanoassemblies have been developed for the treatment of IBD.They exhibit high drug-loading capacities and surmount the challenges posed by poor water solubility and low bioavailability.Notably,phyto-derived nanovesicles,owing to their unique structure and biological functions,can serve as therapeutic agents or novel delivery vehicles for the treatment of IBD.Consequently,this review provides an extensive overview of emerging phytoconstituent-derived nano-medicines/vesicles for the treatment of IBD,intending to offer novel insights for the clinical management of IBD.
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 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.
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 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.
