The dynamic behavior of octahedral gold nanopartides （NPs） and nanoparticle clusters （NPCs） in aqueous solution is studied by in-situ liquid-cell transmission electron microscopy （TEM）. The octahedral Au NPs/NPC...The dynamic behavior of octahedral gold nanopartides （NPs） and nanoparticle clusters （NPCs） in aqueous solution is studied by in-situ liquid-cell transmission electron microscopy （TEM）. The octahedral Au NPs/NPCs show preferential orientations in the liquid cell, due to the interaction with the SiNx window. The Au NPs show long-range reversible hopping and three-dimensional （3D） rotational motions in the liquid environment. At the same time, the Au NPCs and NPs perform slow stick-sUp and stick-roU motions, respectivel~ with a centripetal trend. The centripetal motions were explained by a liquid evaporation-induced radial flow model in which the NPCs/NPs trajectories are controlled by Stokes forces and surface friction by the silicon nitride window. The calculated radius-dependent force （Fc） on the NPCs/NPs shows a semi-linear correlation with the distance r between the NPCs/NPs and the center of mass, accompanied with stochastic fluctuations, in agreement with the model predictions. This work thus demonstrates the effectiveness of in situ liquid-cell TEM for the in-depth understanding of complicated liquid flow and force interactions in nanomaterials.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
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-guest 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
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
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
The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing...The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.展开更多
Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery systems.However,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results ...Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery systems.However,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous injection.The rational design of camptothecins-based prodrug nanoassemblies remains a challenge.Herein,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies.Correspondingly,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical nanoparticles.The length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and pharmacokinetics.Overall,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and tolerance.The findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based 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
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
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
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
Photoimmunotherapy(PIT)is an emerging therapeutic approach that integrates phototherapy and immunotherapy to eliminate primary tumors under an appropriate dosage of local light irradiation,while simultaneously prevent...Photoimmunotherapy(PIT)is an emerging therapeutic approach that integrates phototherapy and immunotherapy to eliminate primary tumors under an appropriate dosage of local light irradiation,while simultaneously preventing tumor metastasis and recurrence by activating the host antitumor immune response.Tumor-responsive dynamic nanoassemblies(TDNs)have evolved from being a mere curiosity to a promising platform for high-performance PIT.However,the dynamic nano-bio interaction between TDNs and tumor microenvironment remains poorly understood,which shall be critical for precise control of TDNs assembling/disassembling behavior and superior PIT efficacy.To deepen the understanding of the structure–function relationship of TDNs,this review introduces the rational design,nano-bio interactions,and controllable functionalities of cutting-edge TDNs for enhanced PIT.Moreover,the synergetic mechanism between TDNs-based PIT and immunomodulatory agents-mediated immunomodulation is particularly emphasized.Finally,the challenges and future perspectives in this emerging field are assessed.展开更多
To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity,and well-defined spatial and temporal resolutions,a facile strategy to prepare u...To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity,and well-defined spatial and temporal resolutions,a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media(nano-XRCM)as dual-modality imaging agents for positron emission tomography(PET)and computed tomography(CT)has been established.Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide)acrylate monomers,the amphiphilic statistical iodocopolymers(ICPs)could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations(>140 mg iodine/mL water)and comparable viscosities to conventional small molecule XRCM.The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca.10 nm in water was confirmed by dynamic and static light scattering techniques.In a breast cancer mouse model,in vivo biodistribution studies revealed that the64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents.PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals,while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection,enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.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
The tremendous potential of triboelectric generators-TENGs for converting mechanical energy into electrical energy places them as one of the most promising energy harvesting technologies. In this work, the fabrication...The tremendous potential of triboelectric generators-TENGs for converting mechanical energy into electrical energy places them as one of the most promising energy harvesting technologies. In this work, the fabrication of enhanced performance TENGs using Ag octahedron nano-assemblies on ITO as electrodes significantly increases the electric charge collection of the induced tribocharges. Thereby, nanostructured electrical contacts coated with Ag macroscale nano-assemblies with octahedral features were obtained by the electrodeposition technique on flexible PET/ITO substrates. Consequently, the nanostructured triboelectric generator-TENG exhibited 65 times more maximum output power, and almost 10 times more open circuit output voltage than that of a TENG with non-nanostructured contacts passing from μW to m W capabilities, which was attributed to the increment of intrinsic interface states due to a higher effective contact area in the former. Likewise, output performances of TENGs also displayed an asymptotic behavior on the output voltage as the operating frequency of the mechanical oscillations increased, which is attributed to a decrement in the internal impedance of the device with frequency. Furthermore, it is shown that the resulting electrical output power can successfully drive low power consumption electronic devices. On that account, the present research establishes a promising platform which contributes in an original way to the development of the TENGs technology.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
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
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
文摘The dynamic behavior of octahedral gold nanopartides （NPs） and nanoparticle clusters （NPCs） in aqueous solution is studied by in-situ liquid-cell transmission electron microscopy （TEM）. The octahedral Au NPs/NPCs show preferential orientations in the liquid cell, due to the interaction with the SiNx window. The Au NPs show long-range reversible hopping and three-dimensional （3D） rotational motions in the liquid environment. At the same time, the Au NPCs and NPs perform slow stick-sUp and stick-roU motions, respectivel~ with a centripetal trend. The centripetal motions were explained by a liquid evaporation-induced radial flow model in which the NPCs/NPs trajectories are controlled by Stokes forces and surface friction by the silicon nitride window. The calculated radius-dependent force （Fc） on the NPCs/NPs shows a semi-linear correlation with the distance r between the NPCs/NPs and the center of mass, accompanied with stochastic fluctuations, in agreement with the model predictions. This work thus demonstrates the effectiveness of in situ liquid-cell TEM for the in-depth understanding of complicated liquid flow and force interactions in nanomaterials.
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-guest 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 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financially supported by National Key R&D Program of China(No.2022YFE0111600)National Natural Science Foundation of China(No.82272151 and 82204318)+2 种基金Doctoral Scientific Research Staring Foundation of Liaoning Province(No.2021-BS-130,China)General Program of Department of Education of Liaoning Province(No.LJKZ0953,China)Shenyang Young and Middle-aged Science and Technology Innovation Talents Support Program(RC220389,China)。
文摘The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.
基金supported by National Natural Science Foundation of China(Nos.82272151,82204318 and 82173766)Doctoral Scientific Research Staring Foundation of Liaoning Province(No.2021-BS-130)+1 种基金General Program of Department of Education of Liaoning Province(No.LJKZ0953)Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220389).
文摘Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery systems.However,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous injection.The rational design of camptothecins-based prodrug nanoassemblies remains a challenge.Herein,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies.Correspondingly,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical nanoparticles.The length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and pharmacokinetics.Overall,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and tolerance.The findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based 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.
基金This work was funded by the National Key Research and Development Program of China(Nos.2022YFB3203804,2022YFB3203801,and 2022YFB3203800)the Leading Talent of“Ten Thousand Plan”-National High-Level Talents Special Support Plan,National Natural Science Foundation of China(Nos.32071374 and 32000985)+4 种基金Program of Shanghai Academic Research Leader under the Science and Technology Innovation Action Plan(No.21XD1422100)Program of Shanghai Science and Technology Development(No.22TS1400700)Zhejiang Provincial Natural Science Foundation of China(Nos.LR22C100001 and LQ21H300003)Innovative Research Team of High-Level Local Universities in Shanghai(No.SHSMUZDCX20210900)CAS Interdisciplinary Innovation Team(No.JCTD-2020-08)。
文摘Photoimmunotherapy(PIT)is an emerging therapeutic approach that integrates phototherapy and immunotherapy to eliminate primary tumors under an appropriate dosage of local light irradiation,while simultaneously preventing tumor metastasis and recurrence by activating the host antitumor immune response.Tumor-responsive dynamic nanoassemblies(TDNs)have evolved from being a mere curiosity to a promising platform for high-performance PIT.However,the dynamic nano-bio interaction between TDNs and tumor microenvironment remains poorly understood,which shall be critical for precise control of TDNs assembling/disassembling behavior and superior PIT efficacy.To deepen the understanding of the structure–function relationship of TDNs,this review introduces the rational design,nano-bio interactions,and controllable functionalities of cutting-edge TDNs for enhanced PIT.Moreover,the synergetic mechanism between TDNs-based PIT and immunomodulatory agents-mediated immunomodulation is particularly emphasized.Finally,the challenges and future perspectives in this emerging field are assessed.
基金financial support from the National Science Foundation(DMR-1905818 and REU Grant CHE1062840,USA)the Robert A.Welch Foundation through the W.T.Doherty-Welch Chair in Chemistry(A-0001,USA)。
文摘To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity,and well-defined spatial and temporal resolutions,a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media(nano-XRCM)as dual-modality imaging agents for positron emission tomography(PET)and computed tomography(CT)has been established.Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide)acrylate monomers,the amphiphilic statistical iodocopolymers(ICPs)could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations(>140 mg iodine/mL water)and comparable viscosities to conventional small molecule XRCM.The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca.10 nm in water was confirmed by dynamic and static light scattering techniques.In a breast cancer mouse model,in vivo biodistribution studies revealed that the64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents.PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals,while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection,enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.
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.
基金Consejo Nacional de Ciencia y Tecnología of México (CONACYT) for her Doctoral scholarshippostgraduate studies department at CIMAVMonterrey for fellowship support。
文摘The tremendous potential of triboelectric generators-TENGs for converting mechanical energy into electrical energy places them as one of the most promising energy harvesting technologies. In this work, the fabrication of enhanced performance TENGs using Ag octahedron nano-assemblies on ITO as electrodes significantly increases the electric charge collection of the induced tribocharges. Thereby, nanostructured electrical contacts coated with Ag macroscale nano-assemblies with octahedral features were obtained by the electrodeposition technique on flexible PET/ITO substrates. Consequently, the nanostructured triboelectric generator-TENG exhibited 65 times more maximum output power, and almost 10 times more open circuit output voltage than that of a TENG with non-nanostructured contacts passing from μW to m W capabilities, which was attributed to the increment of intrinsic interface states due to a higher effective contact area in the former. Likewise, output performances of TENGs also displayed an asymptotic behavior on the output voltage as the operating frequency of the mechanical oscillations increased, which is attributed to a decrement in the internal impedance of the device with frequency. Furthermore, it is shown that the resulting electrical output power can successfully drive low power consumption electronic devices. On that account, the present research establishes a promising platform which contributes in an original way to the development of the TENGs technology.
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.
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.
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.
