Herbicides are indispensable for safeguarding global crop production,yet their effectiveness is often undermined by extensive environmental losses during application.Using herbicide Diuron as a model compound,we devel...Herbicides are indispensable for safeguarding global crop production,yet their effectiveness is often undermined by extensive environmental losses during application.Using herbicide Diuron as a model compound,we developed hierarchical nanoparticles constructed through host-vip molecular recognition followed by electrostatic coassembly,yielding a formulation that unites high delivery efficiency with enhanced environmental compatibility.Relative to conventional wettable powders,these nanoparticles exhibited temperature-responsive release behavior and significantly enhanced foliar adhesion and deposition,increasing leaf retention by more than 241.7%.They also demonstrated strong resistance to rainfall wash-off and a markedly reduced propensity for groundwater leaching,with leaching losses decreased by approximately 18.6%.Greenhouse and field evaluations further confirmed their superior weed control under practical conditions,achieving control efficacies of up to 70.1%against Abutilon theophrasti and 52.9%against Setaria faberi,compared with 53.7%and 39.1%,respectively,for the commercial formulation at the same application rate.Extensive ecotoxicological assessments encompassing seed germination,zebrafish and earthworm assays,in vitro cellular tests,and in vivo rat studies consistently revealed an improved safety profile compared with commercial and technical formulations.Together,these results highlight hierarchical self-assembled nanoparticles as a promising platform for next-generation herbicide delivery that combines high target utilization with lower environmental impact and greater sustainability.展开更多
The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method...The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method can improve the self-assembly phenomenon of Herpetospermum caudigerum Wall.,and the SAN exhibited uniform particle size and demonstrated good stability.In this paper,we analyzed the interactions between the main active compound,herpetrione(Her),and its main carrier,Herpetospermum caudigerum Wall.polysaccharide(HCWP),along with their self-assembly mechanisms under different p H values.The binding constants of Her and HCWP increase with rising p H,leading to the formation of Her-HCWP SAN with a smaller particle size,higher zeta potential,and improved thermal stability.While the contributions of hydrogen bonding and electrostatic attraction to the formation of Her-HCWP SAN increase with rising p H,the hydrophobic force consistently plays a dominant role.This study enhances our scientific understanding of the self-assembly phenomenon of TCM improved by p H driven method.展开更多
The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression.Targeting to different cell populations might result in improved therapeutic effects on malignant tumors.Inte...The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression.Targeting to different cell populations might result in improved therapeutic effects on malignant tumors.Integrins high express on many kinds of tumor cells,and VEGF has a strong effect on tumor angiogenesis.Therefore,based on tumor cells and angiogenesis,we fabricated integrin-targeting cRGD-DOX nanoparticles and combined them with the anti-VEGF antibody bevacizumab.We evaluated the antitumor effect of this combination therapy in an integrin-overexpressing MDA-MB-231 tumor model.The cRGD-DOX nanoparticles were effectively uptake by MDA-MB-231 cells and the uptake was related to the expression of integrinin;cRGD-DOX nanoparticles showed less cytotoxic than free DOX;Bevacizumab did not show significant cytotoxicity against MDA-MB-231 cells at concentrations less than 1 mg/mL.The in vivo results showed that bevacizumab could reduce tumor interstitial fluid pressure;the combination of bevacizumab and cRGD-DOX nanoparticles showed enhanced antitumor effects compared with the corresponding single-agent treatments.These findings suggested the combination of angiogenesis antibody and integrin-targeting nanoparticle loaded with a cytotoxic drug was a promising cancer treatment regimen.展开更多
Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solu...Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects.To solve the problems,we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug,poly[oligo(ethylene glycol)methyl ether methacrylate]-b-poly(oleanolic acid methacrylate)(POEGMA-b-POAMA),encapsulating 10-hydroxycamptothecin(HCPT)to achieve efficient cancer therapy.The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization(RAFT),and could selfassemble to prepare POEGMA-b-POAMA/HCPT nanoparticles(NPs).The obtained nanoparticles exhibited appropriate particle size,excellent drug stability,good drug loading capacity,and high drug loading efficiency.In vitro drug release indicated that the drug release was prolonged to 132 h.The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells.Furthermore,in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor.Therefore,POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.展开更多
Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldru...Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan（FACMCS）nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5：2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties.展开更多
Chitosan was modified by conjugating coupling with linolenic acid through the 1-ethyl-3-（3-dimethylami- nopropyyl） carbodiimide （EDC）-mediated reaction. The degree of substitution 1.8% （ i.e. 1.8 linolenic acid g...Chitosan was modified by conjugating coupling with linolenic acid through the 1-ethyl-3-（3-dimethylami- nopropyyl） carbodiimide （EDC）-mediated reaction. The degree of substitution 1.8% （ i.e. 1.8 linolenic acid group per 100 anhydroglucose units） was measured by ^1H NMR. The critical aggregation concentration （CAC） of the self-aggregate of hydrophobically modified chitosan was determined by measuring the fluorescence intensity of the pyrene as a fluorescent probe. The CAC value in phosphate-buffered saline （PBS） solution （pH 7.4） was 5 × 10^-2 mg mL^-1. The average particle size of selfaggregates of hydrophobically modified chitosan in PBS solution （pH7.4） was 210.8 nm with a unimodal size distribution ranging from 100 to 500 nm. Transmission electron microscopy （TEM） study showed that the formation of near spherical shape nanoparticles has enough structural integrity. The loading ability of hydrophibically modified chitosan （LA-chitosan） was investigated by using bovine serum albumin （BSA） as the model. The loading capacity of self-aggregated nanoparticles increases （ 19.85 % ± 0.04 % to 37.57 % ± 0.25 % ） with the concentration of BSA （0.1-0.5 mg mL^-1 ）.展开更多
Acne vulgaris ranks as the second most prevalent dermatological condition worldwide,and there are still insufficient safe and reliable drugs to treat it.Cryptotanshinone(CTS),a bioactive compound derived from traditio...Acne vulgaris ranks as the second most prevalent dermatological condition worldwide,and there are still insufficient safe and reliable drugs to treat it.Cryptotanshinone(CTS),a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza,has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties.Nevertheless,its local application is hindered by its low solubility and poor skin permeability.To overcome these challenges,a carrierfree pure drug self-assembled nanosystem is employed,which can specifically modify drug molecules based on the disease type and microenvironment,offering a potential for more effective treatment.We designed and synthesized three distinct structures of cationic CTS-peptide conjugates,creating self-assembled nanoparticles.This study has explored their self-assembly behavior,skin permeation,cellular uptake,and both in vitro and in vivo anti-acne effects.Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding andπ-πstacking interactions.Notably,self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates.Furthermore,the nanoparticles exhibited superior anti-acne effects compared to the parent drug,attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway,leading to reduced expression of pro-inflammatory factors including TNF-α,IL-1βand IL-8.In summary,the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability,offering a promising new approach for acne treatment.展开更多
Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobia...Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobial phototherapy in complex microenvironments.Herein,we report a substituen cationization design strategy that not only improves the hydrophilicity of the prepared phthalocyanine molecule,but also promotes the electron transfer process in the photosensitizer,resulting in the strong type I photodynamic effect of the phthalocyanine self-assembled photosensitizer to efficiently generate O_(2)^(·-)under both normal and hypoxic conditions.This in combination with its excellent bacteria recogni tion capability derived from the cationic part on its surface and intrinsic photothermal therapy effect o the phthalocyanine macrocycle endows the phthalocyanine self-assembled photosensitizer with excellen phototherapeutic antimicrobial properties in preclinical models,effectively promoting the wound healing process.This work provides a promising strategy for designing efficient multi-mode photosensitizers.展开更多
Advanced atherosclerosis is the major global cause of death,as featured by the aggregation of apoptotic cells(ACs)in necrotic cores.The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are t...Advanced atherosclerosis is the major global cause of death,as featured by the aggregation of apoptotic cells(ACs)in necrotic cores.The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis.In this study,we constructed self-assembled procyanidins(PC)NPs for loading pitavastatin(Pita).The designed HA@PC@Pita NPs with hyaluronic acid(HA)modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC.In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages.Simultaneously,HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy,a selective autophagy of lipid droplets.In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE^(-/-)mice model with advanced atherosclerosis.Taken together,this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.展开更多
Recently,stimuli-responsive nanocarriers capable of precision drug release have garnered significant attention in the field of drug delivery.Here,an in-situ dynamic covalent self-assembled(DCS)strategy was utilized to...Recently,stimuli-responsive nanocarriers capable of precision drug release have garnered significant attention in the field of drug delivery.Here,an in-situ dynamic covalent self-assembled(DCS)strategy was utilized to develop a co-delivery system.This assembly was based on a thiol-disulfide-exchange reaction,producing disulfide macrocycles in an oxidizing aerial environment.These macrocycles encapsulated the anti-cancer drug(paclitaxel,PTX)on the surface of gold nanoparticles,which served as photothermal therapy agents during the self-assembly.In the DCS process,the kinetic control over the concentration of each building unit within the reaction system led to the formation of a stable co-delivery nanosystem with optimal drug-loading efficiency.Notably,the high glutathione(GSH)concentrations in tumor cells caused the disulfide macrocycles in nanostructures to break,resulting in drug release.The stimuli-responsive performances of the prepared nanosystems were determined by observing the molecular structures and drug release.The results revealed that the self-assembled nanosystem exhibited GSH-triggered drug release and good photothermal conversion capability under near-infrared light.Moreover,the in vitro and in vivo results revealed that conjugating the targeting molecule of cRGD with co-delivery nanosystem enhanced its biocompatibility,chemo-photothermal anti-cancer effect.Overall,our findings indicated that in-situ DCS strategy enhanced the control over drug loading during the construction of the co-delivery system,paving a way for the development of more functional carriers in nanomedicine.展开更多
Lysine-targeting reversible covalent inhibitors,particularly salicylaldehyde-based compounds such as the Food and Drug Administration(FDA)-approved drug Voxelotor,exhibit significant therapeutic potential but are limi...Lysine-targeting reversible covalent inhibitors,particularly salicylaldehyde-based compounds such as the Food and Drug Administration(FDA)-approved drug Voxelotor,exhibit significant therapeutic potential but are limited by challenges including instability and off-target effects.To overcome these limitations in kinase inhibitor A5,we devised a pH-responsive prodrug strategy by masking its reactive aldehyde group with an acid-labile hydrazone linkage and enhancing intracellular delivery through conjugation with FK506.The optimized prodrug demonstrated robust antitumor efficacy in K562 tumor-bearing mice.Furthermore,the incorporation of the photosensitizer chlorin e6(Ce6)led to the formation of self-assembled nanoparticles(AKNP),which not only improved physiological stability and prolonged tumor retention but also enabled light-triggered release of A5 in conjunction with photodynamic therapy(PDT).Our study thus presents a promising prodrug self-assembly strategy that combines the on-demand release of a novel lysine-targeting,reversible covalent kinase inhibitor with PDT in clinical cancer therapy.展开更多
In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was syn...In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobicaUy modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UVNis spectrophotometer. The release profile was heavily pH-dependent around phvsiological pH, and the release rate was significantly enhanced under pH of 6.8.展开更多
Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspire...Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspired by the nanostructure of collagen fibrils,we developed a strategy toward achieving a soft but tough,anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles.Specifically,the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan(HM)with laponite(LAP)to form nanoparticles,followed by the inter-nanoparticle bonding through photo-crosslinking.The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques.Due to the unique structure of the crosslinked nanoparticles,the nanocomposite hydrogels exhibited low stiffness(G’<2 kPa),high compressive strength(709 kPa),and anti-swelling(swelling ratio of 1.07 in PBS)properties.Additionally,by harnessing the photo-crosslinking ability of the nanoparticles,the nanocomposite hydrogels were processed as microgels,which can be three-dimensionally(3D)printed into complex shapes.Furthermore,we demonstrated that these nanocomposite hydrogels are highly biocompatible,biodegradability,and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing.This work presents a promising approach to develop biomimetic,nanofibrillar soft hydrogels for regenerative medicine applications.展开更多
The poor prognosis of triple negative breast cancer(TNBC)results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis,which is associated with high recurrence and short overa...The poor prognosis of triple negative breast cancer(TNBC)results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis,which is associated with high recurrence and short overall survival.Here we developed a strategy by employing tumor-targeted selfassembled nanoparticles to coordinately regulate BACH1(BTB domain and CNC homology 1)and mitochondrial metabolism.The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative(BD)were used to prepare nanoparticles(BH NPs)followed by the modification of chondroitin sulfate(CS)on the surface of BH NPs to achieve tumor targeting(CS/BH NPs).CS/BH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites,glycolysis and metastasis-associated proteins,which were related to the inhibition of BACH1 function.Meanwhile,decreased mitochondrial membrane potential,activated caspase 3/9 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism.In a xenograft mice model of breast cancer,CS/BH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs.In sum,the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CS/BH nanoparticles for the treatment of TNBC.展开更多
The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion...The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.展开更多
Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availabilit...Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availability of numerous therapeutic agents,limitations exhibit,including poor aqueous solubility,suboptimal stability,inadequate permeability,short half-lives,and multi-organ toxicity during long-term or high-dose administration.Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design.This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms.It details the design rationales,therapeutic principles,and effects of various delivery systems,with particular emphasis on their interactions with the disease microenvironment and the entire body.展开更多
An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
Graphitic carbon nitride(g-CN)stands out as the most promising candidate for solar energy conversion owing to its easy preparation,metal-free nature,flexible molecular structure,moderate bandgap,and excellent thermal/...Graphitic carbon nitride(g-CN)stands out as the most promising candidate for solar energy conversion owing to its easy preparation,metal-free nature,flexible molecular structure,moderate bandgap,and excellent thermal/chemical stability.To enhance the performance of intrinsic g-CN,a supramolecular self-assembly strategy has been proposed to regulate the molecular structure of supramolecular precursors through non-covalent interactions across molecular building blocks,thereby optimizing the electronic structure of g-CN.This review provides a comprehensive overview of the recent progress in supramolecular self-assembly-derived graphitic carbon nitride(SM-CN)from both experimental and theoretical computational research in synthesis strategies,including synthesis methods and influencing factors,providing a theoretical foundation for the design of supramolecular assembly.It also discusses modification strategies,such as internal modification of the conjugated plane,interlayer optimization,and construction of heterointerfaces to improve the electronic structure of SM-CN owing to its unique layered structure.This review further summarizes the applications of SM-CN in environment and energy,including wastewater treatment,sterilization and disinfection/air purification,water splitting,H_(2)O_(2)production,organic synthesis/biomass conversion,CO_(2)reduction,photocatalytic coupling technology.Finally,perspectives and outlooks for the future development of SM-CN aim to inspire further innovation in the design and construction of high-performance SM-CN for broader applications.展开更多
基金supported by the University Synergy Innovation Program of Anhui Province(GXXT-2021-059)the National Key Research and Development Program of China(2023YFD1702102)the Major Natural Science Research Project of Anhui Universities(2023AH040143).
文摘Herbicides are indispensable for safeguarding global crop production,yet their effectiveness is often undermined by extensive environmental losses during application.Using herbicide Diuron as a model compound,we developed hierarchical nanoparticles constructed through host-vip molecular recognition followed by electrostatic coassembly,yielding a formulation that unites high delivery efficiency with enhanced environmental compatibility.Relative to conventional wettable powders,these nanoparticles exhibited temperature-responsive release behavior and significantly enhanced foliar adhesion and deposition,increasing leaf retention by more than 241.7%.They also demonstrated strong resistance to rainfall wash-off and a markedly reduced propensity for groundwater leaching,with leaching losses decreased by approximately 18.6%.Greenhouse and field evaluations further confirmed their superior weed control under practical conditions,achieving control efficacies of up to 70.1%against Abutilon theophrasti and 52.9%against Setaria faberi,compared with 53.7%and 39.1%,respectively,for the commercial formulation at the same application rate.Extensive ecotoxicological assessments encompassing seed germination,zebrafish and earthworm assays,in vitro cellular tests,and in vivo rat studies consistently revealed an improved safety profile compared with commercial and technical formulations.Together,these results highlight hierarchical self-assembled nanoparticles as a promising platform for next-generation herbicide delivery that combines high target utilization with lower environmental impact and greater sustainability.
基金supported by the National Natural Science Foundation of China(Nos.81873092,82174074)。
文摘The self-assembled nanoparticles(SAN)formed during the decoction process of traditional Chinese medicine(TCM)exhibit non-uniform particle sizes and a tendency for aggregation.Our group found that the p H-driven method can improve the self-assembly phenomenon of Herpetospermum caudigerum Wall.,and the SAN exhibited uniform particle size and demonstrated good stability.In this paper,we analyzed the interactions between the main active compound,herpetrione(Her),and its main carrier,Herpetospermum caudigerum Wall.polysaccharide(HCWP),along with their self-assembly mechanisms under different p H values.The binding constants of Her and HCWP increase with rising p H,leading to the formation of Her-HCWP SAN with a smaller particle size,higher zeta potential,and improved thermal stability.While the contributions of hydrogen bonding and electrostatic attraction to the formation of Her-HCWP SAN increase with rising p H,the hydrophobic force consistently plays a dominant role.This study enhances our scientific understanding of the self-assembly phenomenon of TCM improved by p H driven method.
基金National Natural Science Foundation of China(Grant No.81690264)the National Key Research and Development Program of China(Grant No.2017YFA0205600)Beijing Natural Science Foundation(Grant No.7162108)
文摘The interplay among diverse cell populations in the tumor microenvironment contributes to tumor progression.Targeting to different cell populations might result in improved therapeutic effects on malignant tumors.Integrins high express on many kinds of tumor cells,and VEGF has a strong effect on tumor angiogenesis.Therefore,based on tumor cells and angiogenesis,we fabricated integrin-targeting cRGD-DOX nanoparticles and combined them with the anti-VEGF antibody bevacizumab.We evaluated the antitumor effect of this combination therapy in an integrin-overexpressing MDA-MB-231 tumor model.The cRGD-DOX nanoparticles were effectively uptake by MDA-MB-231 cells and the uptake was related to the expression of integrinin;cRGD-DOX nanoparticles showed less cytotoxic than free DOX;Bevacizumab did not show significant cytotoxicity against MDA-MB-231 cells at concentrations less than 1 mg/mL.The in vivo results showed that bevacizumab could reduce tumor interstitial fluid pressure;the combination of bevacizumab and cRGD-DOX nanoparticles showed enhanced antitumor effects compared with the corresponding single-agent treatments.These findings suggested the combination of angiogenesis antibody and integrin-targeting nanoparticle loaded with a cytotoxic drug was a promising cancer treatment regimen.
基金This work was financially supported by the National Natural Science Foundation of China(No.21576029)National Key R&D Program of China(No.2017YFD0601205).
文摘Oleanolic acid(OA)is a pentacyclic triterpenoid compound with extensive biological effects,such as anti-inflammatory and anticancer activities.However,the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects.To solve the problems,we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug,poly[oligo(ethylene glycol)methyl ether methacrylate]-b-poly(oleanolic acid methacrylate)(POEGMA-b-POAMA),encapsulating 10-hydroxycamptothecin(HCPT)to achieve efficient cancer therapy.The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization(RAFT),and could selfassemble to prepare POEGMA-b-POAMA/HCPT nanoparticles(NPs).The obtained nanoparticles exhibited appropriate particle size,excellent drug stability,good drug loading capacity,and high drug loading efficiency.In vitro drug release indicated that the drug release was prolonged to 132 h.The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells.Furthermore,in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor.Therefore,POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications.
基金Funded by the National Natural Science Foundation of China(No.50973088)
文摘Nanoparticles conjugated with antibody were designed as active drug delivery system to reduce the toxicity and side effects of drugs for acute myeloid leukemia（AML）.Moreover,methotrexate（MTX）was chosen as modeldrug and encapsulate within folic acid modified carboxymethylchitosan（FACMCS）nanoparticles through self-assembling.The chemicalstructure,morphology,release and targeting of nanoparticles were characterized by routine detection.It is demonstrated that the mean diameter is about 150 nm,the release rate increases with the decreasing of p H,the binding rate of CD33 antibody and FA-CMCS nanoparticles is about 5：2,and nanoparticles can effectively bind onto HL60 cells in vitro.The experimentalresults indicate that the FA-CMCS nanoparticles conjugated with antibody may be used as a potentialp Hsensitive drug delivery system with leukemic targeting properties.
基金National Natural Science Foundation of China(30370344)Korea Science and Engineering Foundation(19992-220-009-4)supported this study
文摘Chitosan was modified by conjugating coupling with linolenic acid through the 1-ethyl-3-（3-dimethylami- nopropyyl） carbodiimide （EDC）-mediated reaction. The degree of substitution 1.8% （ i.e. 1.8 linolenic acid group per 100 anhydroglucose units） was measured by ^1H NMR. The critical aggregation concentration （CAC） of the self-aggregate of hydrophobically modified chitosan was determined by measuring the fluorescence intensity of the pyrene as a fluorescent probe. The CAC value in phosphate-buffered saline （PBS） solution （pH 7.4） was 5 × 10^-2 mg mL^-1. The average particle size of selfaggregates of hydrophobically modified chitosan in PBS solution （pH7.4） was 210.8 nm with a unimodal size distribution ranging from 100 to 500 nm. Transmission electron microscopy （TEM） study showed that the formation of near spherical shape nanoparticles has enough structural integrity. The loading ability of hydrophibically modified chitosan （LA-chitosan） was investigated by using bovine serum albumin （BSA） as the model. The loading capacity of self-aggregated nanoparticles increases （ 19.85 % ± 0.04 % to 37.57 % ± 0.25 % ） with the concentration of BSA （0.1-0.5 mg mL^-1 ）.
文摘Acne vulgaris ranks as the second most prevalent dermatological condition worldwide,and there are still insufficient safe and reliable drugs to treat it.Cryptotanshinone(CTS),a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza,has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties.Nevertheless,its local application is hindered by its low solubility and poor skin permeability.To overcome these challenges,a carrierfree pure drug self-assembled nanosystem is employed,which can specifically modify drug molecules based on the disease type and microenvironment,offering a potential for more effective treatment.We designed and synthesized three distinct structures of cationic CTS-peptide conjugates,creating self-assembled nanoparticles.This study has explored their self-assembly behavior,skin permeation,cellular uptake,and both in vitro and in vivo anti-acne effects.Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding andπ-πstacking interactions.Notably,self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates.Furthermore,the nanoparticles exhibited superior anti-acne effects compared to the parent drug,attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway,leading to reduced expression of pro-inflammatory factors including TNF-α,IL-1βand IL-8.In summary,the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability,offering a promising new approach for acne treatment.
基金supported by the Central Guidance on the Local Science and Technology Development Fund of Guangxi Province(No.Gui Ke ZY22096010)Guangxi Natural Science Fundation(No.2023GXNSFAA026181)+1 种基金National Natural Science Foundation of China(No.51961009)BAGUI Scholar Program,Guangxi Province,China。
文摘Most photodynamic therapies(PDT)rely on reactive oxygen species(ROS)produced by type II mecha nisms.However,since the production of type I ROS is not limited by oxygen content,making it more favorable for antimicrobial phototherapy in complex microenvironments.Herein,we report a substituen cationization design strategy that not only improves the hydrophilicity of the prepared phthalocyanine molecule,but also promotes the electron transfer process in the photosensitizer,resulting in the strong type I photodynamic effect of the phthalocyanine self-assembled photosensitizer to efficiently generate O_(2)^(·-)under both normal and hypoxic conditions.This in combination with its excellent bacteria recogni tion capability derived from the cationic part on its surface and intrinsic photothermal therapy effect o the phthalocyanine macrocycle endows the phthalocyanine self-assembled photosensitizer with excellen phototherapeutic antimicrobial properties in preclinical models,effectively promoting the wound healing process.This work provides a promising strategy for designing efficient multi-mode photosensitizers.
基金supported by the Open Program of NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Yinchuan,Chinathe Natural Science Foundation of Hunan Province(2022JJ40698,China)+2 种基金the National Natural Science Foundation of China for Regional Projects(82060264,82260142)Key Research and Development Projects in Ningxia Province(2018BEG02004,China)The“Phoenix Introduction Plan”Talent Startover Project of The Second Affiliated Hospital of Air Force Medical University(2023YFJH011,China).
文摘Advanced atherosclerosis is the major global cause of death,as featured by the aggregation of apoptotic cells(ACs)in necrotic cores.The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis.In this study,we constructed self-assembled procyanidins(PC)NPs for loading pitavastatin(Pita).The designed HA@PC@Pita NPs with hyaluronic acid(HA)modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC.In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages.Simultaneously,HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy,a selective autophagy of lipid droplets.In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE^(-/-)mice model with advanced atherosclerosis.Taken together,this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.
基金supported by the National Natural Science Foundation of China(Nos.82202274,82072032,22161016,32025021,12374390,52002380 and 31971292),the National Science and Technology Major Project(No.2023ZD0500902)the Fellowship of China Postdoctoral Science Foundation(No.2023M743559)+2 种基金the Member of Youth Innovation Promotion Association Foundation of CAS,China(No.2023310)the Key Scientific and Technological Special Project of Ningbo City(No.2023Z209)the Natural Science Foundation of Zhejiang Province(No.LQ23H180003)。
文摘Recently,stimuli-responsive nanocarriers capable of precision drug release have garnered significant attention in the field of drug delivery.Here,an in-situ dynamic covalent self-assembled(DCS)strategy was utilized to develop a co-delivery system.This assembly was based on a thiol-disulfide-exchange reaction,producing disulfide macrocycles in an oxidizing aerial environment.These macrocycles encapsulated the anti-cancer drug(paclitaxel,PTX)on the surface of gold nanoparticles,which served as photothermal therapy agents during the self-assembly.In the DCS process,the kinetic control over the concentration of each building unit within the reaction system led to the formation of a stable co-delivery nanosystem with optimal drug-loading efficiency.Notably,the high glutathione(GSH)concentrations in tumor cells caused the disulfide macrocycles in nanostructures to break,resulting in drug release.The stimuli-responsive performances of the prepared nanosystems were determined by observing the molecular structures and drug release.The results revealed that the self-assembled nanosystem exhibited GSH-triggered drug release and good photothermal conversion capability under near-infrared light.Moreover,the in vitro and in vivo results revealed that conjugating the targeting molecule of cRGD with co-delivery nanosystem enhanced its biocompatibility,chemo-photothermal anti-cancer effect.Overall,our findings indicated that in-situ DCS strategy enhanced the control over drug loading during the construction of the co-delivery system,paving a way for the development of more functional carriers in nanomedicine.
基金supported by the grants from National Key R&D Program of China(No.2022YFA1104800)Shenzhen Science and Technology Program(No.JCYJ20210324124214038)+4 种基金National Natural Science Foundation of China(Nos.52072418,82300016)Natural Science Foundation of Guangdong Province(No.2023A1515140072)Shenzhen Key Laboratory of Neural Cell Reprogramming and Drug Research,Social Development Science and Technology Key Project of Dongguan(No.20231800940512)the National Medical Research Council(NMRC,No.23-0740-A0001)the Ministry of Education(MOE,No.T2EP10222-0002)of Singapore.
文摘Lysine-targeting reversible covalent inhibitors,particularly salicylaldehyde-based compounds such as the Food and Drug Administration(FDA)-approved drug Voxelotor,exhibit significant therapeutic potential but are limited by challenges including instability and off-target effects.To overcome these limitations in kinase inhibitor A5,we devised a pH-responsive prodrug strategy by masking its reactive aldehyde group with an acid-labile hydrazone linkage and enhancing intracellular delivery through conjugation with FK506.The optimized prodrug demonstrated robust antitumor efficacy in K562 tumor-bearing mice.Furthermore,the incorporation of the photosensitizer chlorin e6(Ce6)led to the formation of self-assembled nanoparticles(AKNP),which not only improved physiological stability and prolonged tumor retention but also enabled light-triggered release of A5 in conjunction with photodynamic therapy(PDT).Our study thus presents a promising prodrug self-assembly strategy that combines the on-demand release of a novel lysine-targeting,reversible covalent kinase inhibitor with PDT in clinical cancer therapy.
文摘In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobicaUy modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UVNis spectrophotometer. The release profile was heavily pH-dependent around phvsiological pH, and the release rate was significantly enhanced under pH of 6.8.
基金financially supported in part by the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120038 and 2021A1515012154)the Fundamental Research Funds for the Central Universities(No.2022ZYGXZR105)+3 种基金the National Natural Science Foundation of China(Nos.82072470 and 81871809)the State Key Laboratory of Pulp and Paper Engineering(No.2022C02)supported by the High-performance Computing Platform of Guangxi Universitysupport from the Vice-Chancellor Early Career Professorship Scheme of The Chinese University of Hong Kong.
文摘Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspired by the nanostructure of collagen fibrils,we developed a strategy toward achieving a soft but tough,anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles.Specifically,the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan(HM)with laponite(LAP)to form nanoparticles,followed by the inter-nanoparticle bonding through photo-crosslinking.The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques.Due to the unique structure of the crosslinked nanoparticles,the nanocomposite hydrogels exhibited low stiffness(G’<2 kPa),high compressive strength(709 kPa),and anti-swelling(swelling ratio of 1.07 in PBS)properties.Additionally,by harnessing the photo-crosslinking ability of the nanoparticles,the nanocomposite hydrogels were processed as microgels,which can be three-dimensionally(3D)printed into complex shapes.Furthermore,we demonstrated that these nanocomposite hydrogels are highly biocompatible,biodegradability,and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing.This work presents a promising approach to develop biomimetic,nanofibrillar soft hydrogels for regenerative medicine applications.
基金supported by the National Natural Science Foundation of China(Nos.81973264,82104080 and 81773659)Guangdong Basic and Applied Basic Research Foundation,China(Nos.2020A1515010593,2019A1515011954 and 2021A1515012621)+1 种基金Guangdong Provincial Key Laboratory of Construction Foundation,Sun Yat-sen University(No.2019B030301005,China)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.22qntd4509,China).
文摘The poor prognosis of triple negative breast cancer(TNBC)results from a lack of approved targeted therapies coupled with aggressive proliferation and metastasis,which is associated with high recurrence and short overall survival.Here we developed a strategy by employing tumor-targeted selfassembled nanoparticles to coordinately regulate BACH1(BTB domain and CNC homology 1)and mitochondrial metabolism.The BACH1 inhibitor hemin and mitochondria function inhibitor berberine derivative(BD)were used to prepare nanoparticles(BH NPs)followed by the modification of chondroitin sulfate(CS)on the surface of BH NPs to achieve tumor targeting(CS/BH NPs).CS/BH NPs were found to be able to inhibit tumor migration and invasion by significantly decreasing the amounts of tumor cell metabolites,glycolysis and metastasis-associated proteins,which were related to the inhibition of BACH1 function.Meanwhile,decreased mitochondrial membrane potential,activated caspase 3/9 and increased ROS production demonstrated coordinated regulation of BACH1 and mitochondrial metabolism.In a xenograft mice model of breast cancer,CS/BH NPs significantly inhibited tumor growth and metastasis due to the synergetic effect of hemin and BD without showing obvious toxicities for major organs.In sum,the results of efficacy and safety experiments suggest potential clinical significance of the prepared self-assembled CS/BH nanoparticles for the treatment of TNBC.
基金supported by the Russian Science Foundation(Grant No.24-25-20087 to V.K.)。
文摘The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.
文摘Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availability of numerous therapeutic agents,limitations exhibit,including poor aqueous solubility,suboptimal stability,inadequate permeability,short half-lives,and multi-organ toxicity during long-term or high-dose administration.Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design.This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms.It details the design rationales,therapeutic principles,and effects of various delivery systems,with particular emphasis on their interactions with the disease microenvironment and the entire body.
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
基金supported by the National Natural Science Foundation of China(NSFC No.52271228)the Natural Science Foundation of Shaanxi Province(No.2023-JC-ZD-21)the Doctoral Dissertation Innovation Fund of Xi'an University of Technology(No.101-252072301)。
文摘Graphitic carbon nitride(g-CN)stands out as the most promising candidate for solar energy conversion owing to its easy preparation,metal-free nature,flexible molecular structure,moderate bandgap,and excellent thermal/chemical stability.To enhance the performance of intrinsic g-CN,a supramolecular self-assembly strategy has been proposed to regulate the molecular structure of supramolecular precursors through non-covalent interactions across molecular building blocks,thereby optimizing the electronic structure of g-CN.This review provides a comprehensive overview of the recent progress in supramolecular self-assembly-derived graphitic carbon nitride(SM-CN)from both experimental and theoretical computational research in synthesis strategies,including synthesis methods and influencing factors,providing a theoretical foundation for the design of supramolecular assembly.It also discusses modification strategies,such as internal modification of the conjugated plane,interlayer optimization,and construction of heterointerfaces to improve the electronic structure of SM-CN owing to its unique layered structure.This review further summarizes the applications of SM-CN in environment and energy,including wastewater treatment,sterilization and disinfection/air purification,water splitting,H_(2)O_(2)production,organic synthesis/biomass conversion,CO_(2)reduction,photocatalytic coupling technology.Finally,perspectives and outlooks for the future development of SM-CN aim to inspire further innovation in the design and construction of high-performance SM-CN for broader applications.
