The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostic...The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostics. The advancement of engineering particle design and fabrication is largely supported by a better understanding of how their apparent characteristics(e.g., size and size distribution, surface morphology, colloidal stability, chemical composition) influence their in vivo biological performance, which raises an urgent need for practical nanoformulation methods. Based on turbulent flow mixing and the self-assembly of molecules in fluids, flash technologies emerged as effective bottom-up fabrication strategies for effective nanoformulation. Among the flash technology family, flash nanocomplexation(FNC) is considered a novel and promising candidate that can promote and optimize formulation processes in a precise spatiotemporal manner, thus obtaining excellent fabrication efficiency, reproducibility and expandability. This review presents an overview of recent advances in fabricating drug-delivery nanoparticles using FNC platforms. Firstly, brief introductions to the basic principles of FNC technology were carried out, followed by descriptions of turbulent microvolume mixers that have significantly promoted the efficiency of FNC-based fabrications. Applications of real formulation cases were then categorized according to the self-assembly-driven interactions(including electrostatic interaction, coordination interaction,hydrogen bonding and hydrophobic interaction) and discussed to reveal the progressiveness of fabricating nanoparticles and discuss how its flexibility will provide advances and replenish the philosophy of nanomedicine formulation. In the end, the commercial potential, current limitations, and prospects of FNC technology for nanoformulation will be summarized and discussed.展开更多
Mesoporous titanium nanoparticles(MTNs) have emerged as an important porous semiconductor owning to their large surface area and unique electronic/optical properties. However, the fundamental research for rational man...Mesoporous titanium nanoparticles(MTNs) have emerged as an important porous semiconductor owning to their large surface area and unique electronic/optical properties. However, the fundamental research for rational manufacturing MTNs in a highly scalable manner remains a challenge. In this study, we report a two-step flash nanocomplexation(FNC) approach to large-scalable generate MTNs through the sequential combination of two multi-inlet vortex mixers. By optimizing the concentrated titanium precursor,polyethylene glycol(PEG)-functionalized silane amount and p H, we have been able to produce MTNs with small particle size(31.5 nm), larger surface area(416.9 m^(2)/g) and pore volume(0.59 cm^(3)/g). Different from the traditional MTNs bulk, FNC-produced MTNs exhibited well-controlled manner and exceptional photocatalytic and antibacterial properties. Importantly, the optimized MTNs outperformed commercial P25 not only in protecting ultraviolet A(UVA)-exposed skin, but also in treating P. aeruginosa-infected wound. We believe that the high controllability and scalability of sequential flash nanocomplexation method offers great opportunities in enhancing the performance of mesoporous titanium nanoparticles.展开更多
Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In ...Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.展开更多
In this study,hydrophobically modified phytoglycogen and hydrolyzed zein were utilized to develop biodegradable and redispersible nanocomplexes for encapsulation of various bioactive phytochemicals,including eugenol,t...In this study,hydrophobically modified phytoglycogen and hydrolyzed zein were utilized to develop biodegradable and redispersible nanocomplexes for encapsulation of various bioactive phytochemicals,including eugenol,thymol,carvacrol,trans-cinnamaldehyde,and their mixtures.Comprehensive physicochemical and colloidal characterizations of these nanocomplexes were performed using dynamic light scattering,and Fourier transform infrared and atomic force microscopy,which evaluated their colloidal stability and redispersibility after freeze-drying.In addition,the antioxidant capacities and antimicrobial activities of these various nanoparticles were investigated methodically.The results revealed that the phytochemical-encapsulated nanocomplexes exhibited a particle size ranging from 60 to 70 nm,display-ing a uniform distribution.Additionally,these nanocomplexes demonstrated sustained morphological and colloidal stability over 30-day storage,and after freeze-drying and subsequent redispersion processing.Furthermore,significant improvements in antioxidant and antimicrobial properties in the aqueous phase were observed.These redispersible nanocomplexes from phytoglycogen and zein hold the promising potential to address the limitations and offer practical solutions for expanding their applications in the pharmaceutical and food fields.展开更多
Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiti...Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.展开更多
In this study,intelligent,pH-responsive colorimetric films were prepared by encapsulating anthocyanins in nanocomplexes prepared from glutenin and carboxymethyl chitosan.These nanocomplexes were added to a corn starch...In this study,intelligent,pH-responsive colorimetric films were prepared by encapsulating anthocyanins in nanocomplexes prepared from glutenin and carboxymethyl chitosan.These nanocomplexes were added to a corn starch matrix and used in the freshness monitoring of chilled pork.The effects of anthocyanin-loaded nanocomplexes on the physical,structural,and functional characteristics of the films were investigated.The addition of anthocyanin-loaded nanocomplexes increased the tensile strength,elongation at break,hydrophobicity,and light transmittance of the films while decreasing their water vapor permeability.This is because new hydrogen bonds are formed between the film components,resulting in a more homogeneous and dense structure.The colorimetric film has a significant color response to pH changes.These films were used in experiments on the freshness of chilled pork,in which the pH changes with changing freshness states.The results show that the colorimetric film can monitor changes in the freshness of chilled pork in real time,where orange,pink,and green represent the fresh,secondary fresh,and putrefied states of pork,respectively.Therefore,the intelligent colorimetric film developed in this study has good application potential in the food industry.展开更多
MXenes have attracted great interest in various fields,and pillared MXenes open a new path with larger interlayer spacing.However,the further study of pillared MXenes is blocked at multilayered state due to serious re...MXenes have attracted great interest in various fields,and pillared MXenes open a new path with larger interlayer spacing.However,the further study of pillared MXenes is blocked at multilayered state due to serious restacking phenomenon of few-layered MXene nanosheets.In this work,for the first time,we designed a facile NH4+method to fundamentally solve the restacking issues of MXene nanosheets and succeeded in achieving pillared few-layered MXene.Sn nanocomplex pillared few-layered Ti3C2Tx(STCT)composites were synthesized by introducing atomic Sn nanocomplex into interlayer of pillared few-layered Ti3C2Tx MXenes via pillaring technique.The MXene matrix can inhibit Sn nanocomplex particles agglomeration and serve as conductive network.Meanwhile,the Sn nanocomplex particles can further open the interlayer spacing of Ti3C2Tx during lithiation/delithiation processes and therefore generate extra capacity.Benefiting from the“pillar effect,”the STCT composites can maintain 1016 mAh g^?1 after 1200 cycles at 2000 mA g^?1 and deliver a stable capacity of 680 mAh g^?1 at 5 A g^?1,showing one of the best performances among MXene-based composites.This work will provide a new way for the development of pillared MXenes and their energy storage due to significant breakthrough from multilayered state to few-layered one.展开更多
We herein propose a co-delivery approach where small interference RNA(siRNA)and anticancer chemotherapeutic drug are simultaneously loaded into a single delivery carrier for the combined treatment of breast cancer and...We herein propose a co-delivery approach where small interference RNA(siRNA)and anticancer chemotherapeutic drug are simultaneously loaded into a single delivery carrier for the combined treatment of breast cancer and metastasis prevention.The co-delivery vector is composed of chondroitin sulfate(CS)-coatedβ-cyclodextrin-polyethylenemine polymer,which is capable of loading paclitaxel(PTX)and siRNA simultaneously to form therapeutic nanocomplexes.The nanocomplex,termed as CPPTX-siCD146-CS,is demonstrated to have strong active targeting ability towards CD44-overexpresing breast cancer cells.Moreover,the co-delivery of PTX and siRNA not only effectively inhibits cancer cells proliferation and induces apoptosis,but also well prevents metastasis.Importantly,CP-PTX-siCD146-CS nanocomplexes exhibit stronger cytotoxic effects and anti-metastatic effects on MBA-MD-231 breast cancer cells,in comparison with PTX or siCD146 mono-treatment.The current study defines a potential therapeutic strategy for the combined breast cancer treatment and metastasis prevention from a codelivery perspective.展开更多
Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microen-vironments(TIMEs).To address these unfavorable TIMEs,supplementation with tumor-associated antigens and stimulat...Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microen-vironments(TIMEs).To address these unfavorable TIMEs,supplementation with tumor-associated antigens and stimulation of immune cells at target sites are indispensable for eliciting anti-tumoral immune responses.Pre-vious research has explored the induction of immunotherapy through multiple injections and implants;however,these approaches lack consideration for patient convenience and the implementation of finely tunable immune response control systems to mitigate the side effects of over-inflammatory responses,such as cytokine storms.In this context,we describe a patient-centric nano-gel-nano system capable of sustained generation of tumorassociated antigens and release of adjuvants.This is achieved through the specific delivery of drugs to cancer cells and antigens/adjuvants to immune cells over the long term,maintaining proper concentrations within the tumor site with a single injection.This system demonstrates local immunity against tumors with a single in-jection,enhances the therapeutic efficacy of immune checkpoint blockades,and induces systemic and memory T cell responses,thus minimizing systemic side effects.展开更多
Forming electrostatic nanocomplexes(ENCs)with counter-ions can improve the delivery efficiency of chemotherapy drugs.However,water-soluble chemotherapy drugs like mitoxantrone(MTO),have limited affinity for counter-io...Forming electrostatic nanocomplexes(ENCs)with counter-ions can improve the delivery efficiency of chemotherapy drugs.However,water-soluble chemotherapy drugs like mitoxantrone(MTO),have limited affinity for counter-ions,posing challenges in the creation of stable ENCs.Herein,MTO was connected to fatty alcohols of varying chain lengths(C8,C12,C16)via disulfide bonds,forming hydrophobic prodrugs.We found that conjugating MTO to fatty alcohols significantly improved its affinity for the counter-ion sodium cholesterol sulfate(SCS).Among the designed prodrugs,conjugated to fatty alcohols with longer carbon chain lengths exhibited heightened affinity for SCS,resulting in the formation of more stable ENCs.However,extending the carbon chain also slowed the rate of drug release.Overall,compared with MTO solution,these ENCs demonstrated comparable therapeutic efficacy while causing minimal damage to healthy tissues,especially for MTO-SS-C16 ENCs.Our research provides new insights for constructing stable and safe ENCs for hydrophilic drugs like MTO.展开更多
Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Her...Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Herein,we reported a lipid/PLGA nanocomplex(RDCM)co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1MT to improve immunotherapy of colon cancer.Arginine–glycine–aspartic acid(RGD)as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol(PEG),and programmed cell death-ligand 1(PDL1)peptide inhibitor DPPA(sequence:CPLGVRGK-GGG-d(NYSKPTDRQYHF))was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker.The Ce6 and 1MT were encapsulated in PLGA nanoparticles.The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes.When the nanocomplexes were delivered to tumor,DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding.RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin.Strong immunogenic cell death was induced by 1 O2 generated from Ce6 irradiation under 660 nm laser.1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment.The RDCM facilitated the maturation of dendritic cells,inhibited the activity of IDO,and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice,triggering a robust immunological memory effect,thus effectively preventing tumor metastasis.The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.展开更多
The emerging technique of photoacoustic imaging,especially in the near infra-red(NIR)window,permits high resolution,deep-penetration,clinically reliable sensing.However,few contrast agents are available that can speci...The emerging technique of photoacoustic imaging,especially in the near infra-red(NIR)window,permits high resolution,deep-penetration,clinically reliable sensing.However,few contrast agents are available that can specifically respond to intricate biological environments,and which are biodegradable and biocompatible.Herein,we in troduce a new class of pH-sensitive orga nic photoacoustic con trast age nt that operates in the second NIR window(NIR-II,960-1,700 nm),which is derived from the self-assembled charge-transfer nanocomplex(CTN)by 3,3',5,5'-tetramethylbenzidine(TMB)and its dication structure(TMB++).The unique NIR-ll-responsive CTN can specifically respond to pH change in the physiological range and allows noninvasive and sensitive visualization of the tumor acidic microenvironment(e.g.at pH5)in mice with higher signal-to-noise ratio.The CTN is biodegradable under physiological conditions(e.g.pH 7.4),which alleviates the biosafety concern of nan oparticle accumulati on in vivo.These results clearly show the pote ntial of the TMB/TMB++-based CTN as a promisi ng pH-activated and biodegradable molecular probe for specific tumor photoacoustic imaging in the NIR-II region.展开更多
Protein corona refers to the structure composed of biomolecules adsorbed on the surface of nanomaterials.The study on the effect of the interaction between protein and nanoparticles can provide an important guide for ...Protein corona refers to the structure composed of biomolecules adsorbed on the surface of nanomaterials.The study on the effect of the interaction between protein and nanoparticles can provide an important guide for the application of nanodrug delivery.To provide a reference for the research on fullerene(C60)nanocomplex drug delivery systems,this work studied the interaction between C60 nanocomplex and a variety of plasma proteins.Research showed that the protein binding with C60 nanocomplex did not change the charge properties of protein.The proteins induced the aggregation of C60 nanocomplex.The circular dichroism spectra showed that the secondary structure of the proteins changed after binding to C60 nanocomplex.The ultraviolet-visible spectra showed that the effect of C60 nanocomplex on proteins was concentration-dependent.The fluorescence spectra showed that C60 nanocomplex could intrinsic fluorescence alteration of proteins.The adsorption capacity of C60 nanocomplex to proteins was changed at 0 h and 4 h.The interaction between nanocomplex and proteins might affect the morphological characteristics of nanocomplex and the conformation of proteins.This work could provide a reference for the research and development of C60 nanocomplex and other carbon-based nanocomplex as nanoparticulate drug delivery systems.展开更多
Pterostilbene(PTS)has received considerable attention in recent years because of its beneficial effects on health;however,its poor solubility hinders its application in the food industry.This study aimed to prepare an...Pterostilbene(PTS)has received considerable attention in recent years because of its beneficial effects on health;however,its poor solubility hinders its application in the food industry.This study aimed to prepare and characterise three types of proteins(whey protein isolate(WPI),soybean protein isolate(SPI),and flaxseed protein isolate(FPI))conjugates of PTS,which could improve its solubility and stability.The results showed that the spherical particles of the protein-based nano-complexes were dissociated and homogenous.Proteins bound to PTS mainly through hydrophobic interactions and hydrogen bonding,and PTS in proteins existed in an amorphous state.FPI conferred PTS with better thermal stability than WPI and SPI.Further coating of FPI-PTS with soybean polysaccharide and maltodextrin yielded a more stable nanocomplex structure.The prepared nanocomplex powder exhibited better thermal,illumination,and storage stabilities than FPI-PTS.This study provides guidelines for the potential application of protein-based nano-complexes in functional foods.展开更多
Curcumin, commonly used as a coloring agent as well as food additive, has exhibited great therapeutic efficacy for development of functional foods. In order to expand its applications in food, strategies are needed to...Curcumin, commonly used as a coloring agent as well as food additive, has exhibited great therapeutic efficacy for development of functional foods. In order to expand its applications in food, strategies are needed to tackle the poor water-solubility, bioavailability and bioaccessibility of curcumin. Nanoparticles made from individual biomaterials such as proteins, polysaccharides and lipids have been introduced and their properties have been comprehensively studied. Recently, there has been an increasing interest in nanocomplexes made from two or more biomaterials because of their ability to composite the advantages of various components. This review has specific focus on the nanocomplexes fabricated from proteins and polysaccharides. First, complexation methods with or without chemical covalent bond formation are summarized, while different methods with different degrees of complexation are discussed. The encapsulation strategies of curcumin, both traditional and newly invented, are also compared. Then, the structure and physicochemical properties of the resulting binary or ternary nanocomplexes are discussed in detail, as well as a comparison of the delivery efficiency. Last but not least, the current limitations and future directions in the development of curcumin-loaded biopolymer nanoparticles for the design of future food products are presented.展开更多
In the present study,nanocomplexes composed of perilla seed protein isolate(PSPI)and pectin(PEC)were assembled for the delivery of curcumin(Cur)based on the pH-driven self-assembly method.The encapsulation efficiency ...In the present study,nanocomplexes composed of perilla seed protein isolate(PSPI)and pectin(PEC)were assembled for the delivery of curcumin(Cur)based on the pH-driven self-assembly method.The encapsulation efficiency of Cur was 87.77%,and the PSPI-Cur-PEC exhibited controlled release of Cur during the in vitro digestion.Moreover,the PSPI-Cur-PEC possessed efficient antioxidant activity and provided greater defense for Cur against thermal treatment and ultraviolet irradiation.Fourier transform infrared spectroscopy,fluorescence spectroscopy and X-ray diffraction results indicated that entrapped Cur was existed in the form of amorphous state in PSPI-PEC,and the process was driven by hydrophobic effects,hydrogen bonding and electrostatic in-teractions.Scanning electron microscopy images revealed substantial morphological changes of the nano-complexes throughout the process,while transmission electron microscopy images observed the core-shell structure of PSPI-Cur-PEC nanocomplexes.Furthermore,PSPI-PEC exhibited excellent biocompatibility by the in vitro cytotoxicity assay on Caco-2 cells,and the intermolecular interactions and possible formation mechanism of PSPI-Cur-PEC were further determined by molecular docking.This work elucidated that PSPI-PEC nano-complexes assembled by a green and energy-efficient pH-driven method was feasible to protect sensitive hy-drophobic bioactive components and provided a possible utilization of perilla seed protein in delivery system for nutraceuticals.展开更多
Three nanocomplexes of Cu(II),Co(II),and Ni(II)with theophylline were synthesized by ultrasonic sonication method.This method was used to produce smaller and narrow-distributed nanoparticles without any aggregations.M...Three nanocomplexes of Cu(II),Co(II),and Ni(II)with theophylline were synthesized by ultrasonic sonication method.This method was used to produce smaller and narrow-distributed nanoparticles without any aggregations.Melting point,molar conductivity,solubility,flame atomic absorption,Fourier-transform infrared spectroscopy(FTIR)and elemental analysis(C,H,N,and S)were used to identify and to suggest the structure of the synthesized nanocomplexes.The transmission electron microscopy(TEM)results exhibited that the size of nanocomplexes was in the range of 15-25 nm.The efficacy of the synthesized nanocomplexes was examined against four types of bacterial strains,Staphylococcus aureus,Bacillus subtilis(gram-positive bacteria),and Klebsiella pneumoniae,Escherichia Coli(gram-negative bacteria).The results showed that all nanocomplexes had very high susceptibility to inhibit bacterial growth,as they resulted in an inhibition zone between 98%and 100%.The copper nanocomplex gave the highest inhibition zone by 100%for each type of bacterial strains,due to the surface plasmon.Therefore,a further test for the copper nanocomplex Cu(THP)2(H2O)2(Cl)2 was carried out on skin injuries of laboratory mice after it was converted into cream with vaseline and was found to have a very potent influence in healing skin injuries.展开更多
Copper(Ⅱ)theophylline[Cu(THP)2(H2O)4]complex in nanoscale has synthesized by ultrasonic sonication method.This method was used in the development of smaller,dispersed,and unaggregated nanoparticles(NPs).The structure...Copper(Ⅱ)theophylline[Cu(THP)2(H2O)4]complex in nanoscale has synthesized by ultrasonic sonication method.This method was used in the development of smaller,dispersed,and unaggregated nanoparticles(NPs).The structure of nanocomplex was described and suggested by the molar conductance,Fourier transform infrared spectroscopy(FTIR),ultraviolet-visible spectroscopy(UV-Vis),solubility,atomic fire absorption,and C.H.N.elemental analysis as octahedral geometry.The size and morphology of nanocomplex measured by transmission electron microscopy(TEM)were 20 nm.The nanocomplex was studied on phosphodiesterase enzyme activity in human serum of Iraqi patient›s asthma disease.The results showed a highly significant(p<0.01)increase in the serum levels of phosphodiesterase enzyme activity in asthma patients(mean=14.939±3.021 ng/mL)compared with a control group(mean=9.974±2.032 ng/mL).The result also showed a highly significant(p<0.01)decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with theophylline(mean=11.253±2.479 ng/mL)compared to serum patients without nano and control groups.It is vital that the result showed a highly significant(p<0.01)decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with copper nano complex(mean=9.563±2.082 ng/mL)compared in patients of asthma disease with and without theophylline.As for comparing asthma disease with copper nano complex and control group,the result showed there was no significant effect(p>0.05).展开更多
基金supported by the Sanya Yazhou Bay Science and Technology City (No. 2021JJLH0037)Taishan Scholar Foundation of Shandong Province (No. tsqn202211065)+2 种基金Natural Science Foundation of China (No. 82003673)Yangcheng Scholars Research Project of Guangzhou (No. 20183197)Guangzhou Science and Technology Plan (No. 201901010170)
文摘The application of nanotechnologies in formulation has significantly promoted the development of modern medical and pharmacological science, especially for nanoparticle-based drug delivery, bioimaging, and theranostics. The advancement of engineering particle design and fabrication is largely supported by a better understanding of how their apparent characteristics(e.g., size and size distribution, surface morphology, colloidal stability, chemical composition) influence their in vivo biological performance, which raises an urgent need for practical nanoformulation methods. Based on turbulent flow mixing and the self-assembly of molecules in fluids, flash technologies emerged as effective bottom-up fabrication strategies for effective nanoformulation. Among the flash technology family, flash nanocomplexation(FNC) is considered a novel and promising candidate that can promote and optimize formulation processes in a precise spatiotemporal manner, thus obtaining excellent fabrication efficiency, reproducibility and expandability. This review presents an overview of recent advances in fabricating drug-delivery nanoparticles using FNC platforms. Firstly, brief introductions to the basic principles of FNC technology were carried out, followed by descriptions of turbulent microvolume mixers that have significantly promoted the efficiency of FNC-based fabrications. Applications of real formulation cases were then categorized according to the self-assembly-driven interactions(including electrostatic interaction, coordination interaction,hydrogen bonding and hydrophobic interaction) and discussed to reveal the progressiveness of fabricating nanoparticles and discuss how its flexibility will provide advances and replenish the philosophy of nanomedicine formulation. In the end, the commercial potential, current limitations, and prospects of FNC technology for nanoformulation will be summarized and discussed.
基金supported by the National Natural Science Foundation of China (No.32271388)。
文摘Mesoporous titanium nanoparticles(MTNs) have emerged as an important porous semiconductor owning to their large surface area and unique electronic/optical properties. However, the fundamental research for rational manufacturing MTNs in a highly scalable manner remains a challenge. In this study, we report a two-step flash nanocomplexation(FNC) approach to large-scalable generate MTNs through the sequential combination of two multi-inlet vortex mixers. By optimizing the concentrated titanium precursor,polyethylene glycol(PEG)-functionalized silane amount and p H, we have been able to produce MTNs with small particle size(31.5 nm), larger surface area(416.9 m^(2)/g) and pore volume(0.59 cm^(3)/g). Different from the traditional MTNs bulk, FNC-produced MTNs exhibited well-controlled manner and exceptional photocatalytic and antibacterial properties. Importantly, the optimized MTNs outperformed commercial P25 not only in protecting ultraviolet A(UVA)-exposed skin, but also in treating P. aeruginosa-infected wound. We believe that the high controllability and scalability of sequential flash nanocomplexation method offers great opportunities in enhancing the performance of mesoporous titanium nanoparticles.
基金supported by National Natural Science Foundation of China(Nos.82322015,82171006)Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)+3 种基金Sichuan Science and Technology Program(No.2022NSFSC0002)West China Hospital of Stomatology Sichuan University(No.RCDWJS2024-3)Sichuan Science and Technology Program(Nos.2023NSFSC1706,2024NSFSC1589)Postdoctoral Science Foundation of China(No.BX20220220)。
文摘Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.
基金supported by the U.S.Department of Agriculture(USDA),National Institute of Food and Agriculture,Award No.2022-67018-37143.
文摘In this study,hydrophobically modified phytoglycogen and hydrolyzed zein were utilized to develop biodegradable and redispersible nanocomplexes for encapsulation of various bioactive phytochemicals,including eugenol,thymol,carvacrol,trans-cinnamaldehyde,and their mixtures.Comprehensive physicochemical and colloidal characterizations of these nanocomplexes were performed using dynamic light scattering,and Fourier transform infrared and atomic force microscopy,which evaluated their colloidal stability and redispersibility after freeze-drying.In addition,the antioxidant capacities and antimicrobial activities of these various nanoparticles were investigated methodically.The results revealed that the phytochemical-encapsulated nanocomplexes exhibited a particle size ranging from 60 to 70 nm,display-ing a uniform distribution.Additionally,these nanocomplexes demonstrated sustained morphological and colloidal stability over 30-day storage,and after freeze-drying and subsequent redispersion processing.Furthermore,significant improvements in antioxidant and antimicrobial properties in the aqueous phase were observed.These redispersible nanocomplexes from phytoglycogen and zein hold the promising potential to address the limitations and offer practical solutions for expanding their applications in the pharmaceutical and food fields.
基金funded by grants from the National Natural Science Foundation of China(Grant No.:82274506)the China Postdoctoral Science Foundation(Grant No.:2022M721128)+6 种基金the Science and Technology Innovation Program of Hunan,China(Grant No.:2021RC4035)the Natural Science Foundation of Hunan,China(Grant No.:2023JJ40477)the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine(HNUCM),China(Grant No.:22JBZ003)was financially supported by the Furong Distinguished Scholar Program of Hunan,China(Program No.:XJT[2020]58)the 121 Training Project for Innovative Talents of Hunan,China(Project No.:XRSH[2019]192)the Chinese Academy of Engineering Academician Liang Liu's Workstation Project,China(Project No.:KH[2023]3-23YS001)the World First-class Discipline Incubation Project of HNUCM,China(Project No.:XJF[2022]57)。
文摘Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.
基金funded by the Hainan Provincial Natural Science Foundation of China[Grant Number 2019RC031]National Natural Science Foundation of China[Grant Number 31460407].
文摘In this study,intelligent,pH-responsive colorimetric films were prepared by encapsulating anthocyanins in nanocomplexes prepared from glutenin and carboxymethyl chitosan.These nanocomplexes were added to a corn starch matrix and used in the freshness monitoring of chilled pork.The effects of anthocyanin-loaded nanocomplexes on the physical,structural,and functional characteristics of the films were investigated.The addition of anthocyanin-loaded nanocomplexes increased the tensile strength,elongation at break,hydrophobicity,and light transmittance of the films while decreasing their water vapor permeability.This is because new hydrogen bonds are formed between the film components,resulting in a more homogeneous and dense structure.The colorimetric film has a significant color response to pH changes.These films were used in experiments on the freshness of chilled pork,in which the pH changes with changing freshness states.The results show that the colorimetric film can monitor changes in the freshness of chilled pork in real time,where orange,pink,and green represent the fresh,secondary fresh,and putrefied states of pork,respectively.Therefore,the intelligent colorimetric film developed in this study has good application potential in the food industry.
基金the National Natural Science Foundation of China(Grant No.51901206,51822104)the Training Program of Major Basic Research Project of Provincial Natural Science Foundation of Guangdong(2017B030308001).
文摘MXenes have attracted great interest in various fields,and pillared MXenes open a new path with larger interlayer spacing.However,the further study of pillared MXenes is blocked at multilayered state due to serious restacking phenomenon of few-layered MXene nanosheets.In this work,for the first time,we designed a facile NH4+method to fundamentally solve the restacking issues of MXene nanosheets and succeeded in achieving pillared few-layered MXene.Sn nanocomplex pillared few-layered Ti3C2Tx(STCT)composites were synthesized by introducing atomic Sn nanocomplex into interlayer of pillared few-layered Ti3C2Tx MXenes via pillaring technique.The MXene matrix can inhibit Sn nanocomplex particles agglomeration and serve as conductive network.Meanwhile,the Sn nanocomplex particles can further open the interlayer spacing of Ti3C2Tx during lithiation/delithiation processes and therefore generate extra capacity.Benefiting from the“pillar effect,”the STCT composites can maintain 1016 mAh g^?1 after 1200 cycles at 2000 mA g^?1 and deliver a stable capacity of 680 mAh g^?1 at 5 A g^?1,showing one of the best performances among MXene-based composites.This work will provide a new way for the development of pillared MXenes and their energy storage due to significant breakthrough from multilayered state to few-layered one.
基金supported Fundamental Research Funds for the Central Universities(No.520002^*172210381)。
文摘We herein propose a co-delivery approach where small interference RNA(siRNA)and anticancer chemotherapeutic drug are simultaneously loaded into a single delivery carrier for the combined treatment of breast cancer and metastasis prevention.The co-delivery vector is composed of chondroitin sulfate(CS)-coatedβ-cyclodextrin-polyethylenemine polymer,which is capable of loading paclitaxel(PTX)and siRNA simultaneously to form therapeutic nanocomplexes.The nanocomplex,termed as CPPTX-siCD146-CS,is demonstrated to have strong active targeting ability towards CD44-overexpresing breast cancer cells.Moreover,the co-delivery of PTX and siRNA not only effectively inhibits cancer cells proliferation and induces apoptosis,but also well prevents metastasis.Importantly,CP-PTX-siCD146-CS nanocomplexes exhibit stronger cytotoxic effects and anti-metastatic effects on MBA-MD-231 breast cancer cells,in comparison with PTX or siCD146 mono-treatment.The current study defines a potential therapeutic strategy for the combined breast cancer treatment and metastasis prevention from a codelivery perspective.
基金.The authors also thank M.S.Kyungwoo Lee for his illustration and Dr.Seung Ja Oh,Dr.Hong Yeol Yoon and Yuna Cheon for their fruitful discussions on this work.
文摘Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microen-vironments(TIMEs).To address these unfavorable TIMEs,supplementation with tumor-associated antigens and stimulation of immune cells at target sites are indispensable for eliciting anti-tumoral immune responses.Pre-vious research has explored the induction of immunotherapy through multiple injections and implants;however,these approaches lack consideration for patient convenience and the implementation of finely tunable immune response control systems to mitigate the side effects of over-inflammatory responses,such as cytokine storms.In this context,we describe a patient-centric nano-gel-nano system capable of sustained generation of tumorassociated antigens and release of adjuvants.This is achieved through the specific delivery of drugs to cancer cells and antigens/adjuvants to immune cells over the long term,maintaining proper concentrations within the tumor site with a single injection.This system demonstrates local immunity against tumors with a single in-jection,enhances the therapeutic efficacy of immune checkpoint blockades,and induces systemic and memory T cell responses,thus minimizing systemic side effects.
基金financial support from National Natural Science Foundation of China (82272151,82173766,and 82204318)Liaoning Revitalization Talents Program (XLYC2203083)Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program (RC220389)。
文摘Forming electrostatic nanocomplexes(ENCs)with counter-ions can improve the delivery efficiency of chemotherapy drugs.However,water-soluble chemotherapy drugs like mitoxantrone(MTO),have limited affinity for counter-ions,posing challenges in the creation of stable ENCs.Herein,MTO was connected to fatty alcohols of varying chain lengths(C8,C12,C16)via disulfide bonds,forming hydrophobic prodrugs.We found that conjugating MTO to fatty alcohols significantly improved its affinity for the counter-ion sodium cholesterol sulfate(SCS).Among the designed prodrugs,conjugated to fatty alcohols with longer carbon chain lengths exhibited heightened affinity for SCS,resulting in the formation of more stable ENCs.However,extending the carbon chain also slowed the rate of drug release.Overall,compared with MTO solution,these ENCs demonstrated comparable therapeutic efficacy while causing minimal damage to healthy tissues,especially for MTO-SS-C16 ENCs.Our research provides new insights for constructing stable and safe ENCs for hydrophilic drugs like MTO.
基金supported by the National Natural Science Foundation of China[52073216 and 51773130].
文摘Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Herein,we reported a lipid/PLGA nanocomplex(RDCM)co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1MT to improve immunotherapy of colon cancer.Arginine–glycine–aspartic acid(RGD)as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol(PEG),and programmed cell death-ligand 1(PDL1)peptide inhibitor DPPA(sequence:CPLGVRGK-GGG-d(NYSKPTDRQYHF))was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker.The Ce6 and 1MT were encapsulated in PLGA nanoparticles.The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes.When the nanocomplexes were delivered to tumor,DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding.RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin.Strong immunogenic cell death was induced by 1 O2 generated from Ce6 irradiation under 660 nm laser.1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment.The RDCM facilitated the maturation of dendritic cells,inhibited the activity of IDO,and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice,triggering a robust immunological memory effect,thus effectively preventing tumor metastasis.The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.
基金the financial supports from NTU-AIT-MUV NAM/16001,RG110/16(S),(RG 11/13)and(RG 35/15)awarded in Nanyang Technological University and the National Natural Science Foundation of China(NSFC)(No.51628201).
文摘The emerging technique of photoacoustic imaging,especially in the near infra-red(NIR)window,permits high resolution,deep-penetration,clinically reliable sensing.However,few contrast agents are available that can specifically respond to intricate biological environments,and which are biodegradable and biocompatible.Herein,we in troduce a new class of pH-sensitive orga nic photoacoustic con trast age nt that operates in the second NIR window(NIR-II,960-1,700 nm),which is derived from the self-assembled charge-transfer nanocomplex(CTN)by 3,3',5,5'-tetramethylbenzidine(TMB)and its dication structure(TMB++).The unique NIR-ll-responsive CTN can specifically respond to pH change in the physiological range and allows noninvasive and sensitive visualization of the tumor acidic microenvironment(e.g.at pH5)in mice with higher signal-to-noise ratio.The CTN is biodegradable under physiological conditions(e.g.pH 7.4),which alleviates the biosafety concern of nan oparticle accumulati on in vivo.These results clearly show the pote ntial of the TMB/TMB++-based CTN as a promisi ng pH-activated and biodegradable molecular probe for specific tumor photoacoustic imaging in the NIR-II region.
基金supports from National Natural Science Foundation of China (grant Nos.82073774 and 82104070)。
文摘Protein corona refers to the structure composed of biomolecules adsorbed on the surface of nanomaterials.The study on the effect of the interaction between protein and nanoparticles can provide an important guide for the application of nanodrug delivery.To provide a reference for the research on fullerene(C60)nanocomplex drug delivery systems,this work studied the interaction between C60 nanocomplex and a variety of plasma proteins.Research showed that the protein binding with C60 nanocomplex did not change the charge properties of protein.The proteins induced the aggregation of C60 nanocomplex.The circular dichroism spectra showed that the secondary structure of the proteins changed after binding to C60 nanocomplex.The ultraviolet-visible spectra showed that the effect of C60 nanocomplex on proteins was concentration-dependent.The fluorescence spectra showed that C60 nanocomplex could intrinsic fluorescence alteration of proteins.The adsorption capacity of C60 nanocomplex to proteins was changed at 0 h and 4 h.The interaction between nanocomplex and proteins might affect the morphological characteristics of nanocomplex and the conformation of proteins.This work could provide a reference for the research and development of C60 nanocomplex and other carbon-based nanocomplex as nanoparticulate drug delivery systems.
文摘Pterostilbene(PTS)has received considerable attention in recent years because of its beneficial effects on health;however,its poor solubility hinders its application in the food industry.This study aimed to prepare and characterise three types of proteins(whey protein isolate(WPI),soybean protein isolate(SPI),and flaxseed protein isolate(FPI))conjugates of PTS,which could improve its solubility and stability.The results showed that the spherical particles of the protein-based nano-complexes were dissociated and homogenous.Proteins bound to PTS mainly through hydrophobic interactions and hydrogen bonding,and PTS in proteins existed in an amorphous state.FPI conferred PTS with better thermal stability than WPI and SPI.Further coating of FPI-PTS with soybean polysaccharide and maltodextrin yielded a more stable nanocomplex structure.The prepared nanocomplex powder exhibited better thermal,illumination,and storage stabilities than FPI-PTS.This study provides guidelines for the potential application of protein-based nano-complexes in functional foods.
文摘Curcumin, commonly used as a coloring agent as well as food additive, has exhibited great therapeutic efficacy for development of functional foods. In order to expand its applications in food, strategies are needed to tackle the poor water-solubility, bioavailability and bioaccessibility of curcumin. Nanoparticles made from individual biomaterials such as proteins, polysaccharides and lipids have been introduced and their properties have been comprehensively studied. Recently, there has been an increasing interest in nanocomplexes made from two or more biomaterials because of their ability to composite the advantages of various components. This review has specific focus on the nanocomplexes fabricated from proteins and polysaccharides. First, complexation methods with or without chemical covalent bond formation are summarized, while different methods with different degrees of complexation are discussed. The encapsulation strategies of curcumin, both traditional and newly invented, are also compared. Then, the structure and physicochemical properties of the resulting binary or ternary nanocomplexes are discussed in detail, as well as a comparison of the delivery efficiency. Last but not least, the current limitations and future directions in the development of curcumin-loaded biopolymer nanoparticles for the design of future food products are presented.
基金supported by the Discipline-Team of Northeast Agri-cultural University,“Storage,processing and demonstration of charac-teristic fruits and vegetables”(107-54941312)the“Research and development of Perilla series products’related technologies”from en-terprise cooperationand the“Young Talents”Project of Northeast Agricultural University(206-54980112).
文摘In the present study,nanocomplexes composed of perilla seed protein isolate(PSPI)and pectin(PEC)were assembled for the delivery of curcumin(Cur)based on the pH-driven self-assembly method.The encapsulation efficiency of Cur was 87.77%,and the PSPI-Cur-PEC exhibited controlled release of Cur during the in vitro digestion.Moreover,the PSPI-Cur-PEC possessed efficient antioxidant activity and provided greater defense for Cur against thermal treatment and ultraviolet irradiation.Fourier transform infrared spectroscopy,fluorescence spectroscopy and X-ray diffraction results indicated that entrapped Cur was existed in the form of amorphous state in PSPI-PEC,and the process was driven by hydrophobic effects,hydrogen bonding and electrostatic in-teractions.Scanning electron microscopy images revealed substantial morphological changes of the nano-complexes throughout the process,while transmission electron microscopy images observed the core-shell structure of PSPI-Cur-PEC nanocomplexes.Furthermore,PSPI-PEC exhibited excellent biocompatibility by the in vitro cytotoxicity assay on Caco-2 cells,and the intermolecular interactions and possible formation mechanism of PSPI-Cur-PEC were further determined by molecular docking.This work elucidated that PSPI-PEC nano-complexes assembled by a green and energy-efficient pH-driven method was feasible to protect sensitive hy-drophobic bioactive components and provided a possible utilization of perilla seed protein in delivery system for nutraceuticals.
基金supported by Department of Chemistry,College of Science,Mustansiriyah University.
文摘Three nanocomplexes of Cu(II),Co(II),and Ni(II)with theophylline were synthesized by ultrasonic sonication method.This method was used to produce smaller and narrow-distributed nanoparticles without any aggregations.Melting point,molar conductivity,solubility,flame atomic absorption,Fourier-transform infrared spectroscopy(FTIR)and elemental analysis(C,H,N,and S)were used to identify and to suggest the structure of the synthesized nanocomplexes.The transmission electron microscopy(TEM)results exhibited that the size of nanocomplexes was in the range of 15-25 nm.The efficacy of the synthesized nanocomplexes was examined against four types of bacterial strains,Staphylococcus aureus,Bacillus subtilis(gram-positive bacteria),and Klebsiella pneumoniae,Escherichia Coli(gram-negative bacteria).The results showed that all nanocomplexes had very high susceptibility to inhibit bacterial growth,as they resulted in an inhibition zone between 98%and 100%.The copper nanocomplex gave the highest inhibition zone by 100%for each type of bacterial strains,due to the surface plasmon.Therefore,a further test for the copper nanocomplex Cu(THP)2(H2O)2(Cl)2 was carried out on skin injuries of laboratory mice after it was converted into cream with vaseline and was found to have a very potent influence in healing skin injuries.
基金supported by the Chemistry Department,college of science,Mustansiriyah University.
文摘Copper(Ⅱ)theophylline[Cu(THP)2(H2O)4]complex in nanoscale has synthesized by ultrasonic sonication method.This method was used in the development of smaller,dispersed,and unaggregated nanoparticles(NPs).The structure of nanocomplex was described and suggested by the molar conductance,Fourier transform infrared spectroscopy(FTIR),ultraviolet-visible spectroscopy(UV-Vis),solubility,atomic fire absorption,and C.H.N.elemental analysis as octahedral geometry.The size and morphology of nanocomplex measured by transmission electron microscopy(TEM)were 20 nm.The nanocomplex was studied on phosphodiesterase enzyme activity in human serum of Iraqi patient›s asthma disease.The results showed a highly significant(p<0.01)increase in the serum levels of phosphodiesterase enzyme activity in asthma patients(mean=14.939±3.021 ng/mL)compared with a control group(mean=9.974±2.032 ng/mL).The result also showed a highly significant(p<0.01)decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with theophylline(mean=11.253±2.479 ng/mL)compared to serum patients without nano and control groups.It is vital that the result showed a highly significant(p<0.01)decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with copper nano complex(mean=9.563±2.082 ng/mL)compared in patients of asthma disease with and without theophylline.As for comparing asthma disease with copper nano complex and control group,the result showed there was no significant effect(p>0.05).
