Magnetic microbubble:A biomedical platform co-constructed from magnetics and acoustics

Generation of magnetic micrbubbles and their basic magnetic and acoustic mechanism are reviewed. The ultrasound （US） and magnetic resonance （MR） dual imaging, the controlled therapeutic delivery, as well as theranostic multifunctions are all introduced based on recent research results. Some on-going research is also discussed.

Antibacterial Chemodynamic Therapy: Materials and Strategies

The wide and frequent use of antibiotics in the treatment of bacterial infection can cause the occurrence of multidrug-resistant bacteria,which becomes a serious health threat.Therefore,it is necessary to develop antibiotic-independent treatment modalities.Chemodynamic therapy(CDT)is defined as the approach employing Fenton and/or Fenton-like reactions for generating hydroxyl radical(•OH)that can kill target cells.Recently,CDT has been successfully employed for antibacterial applications.Apart from the common Fe-mediated CDT strategy,antibacterial CDT strategies mediated by other metal elements such as copper,manganese,cobalt,molybdenum,platinum,tungsten,nickel,silver,ruthenium,and zinc have also been proposed.Furthermore,different types of materials like nanomaterials and hydrogels can be adopted for constructing CDT-involved antibacterial platforms.Besides,CDT can introduce some toxic metal elements and then achieve synergistic antibacterial effects together with reactive oxygen species.Finally,CDT can be combined with other therapies such as starvation therapy,phototherapy,and sonodynamic therapy for achieving improved antibacterial performance.This review first summarizes the advancements in antibacterial CDT and then discusses the present limitations and future research directions in this field,hoping to promote the development of more effective materials and strategies for achieving potentiated CDT.

Enhancing osteogenic bioactivities of coaxial electrospinning nanoscaffolds through incorporating iron oxide nanoparticles and icaritin for bone regeneration

Bone tissue engineering provides a promising strategy for the treatment of bone defects.Nonetheless,the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive properties.Here,we proposed to endow nano-scaffold(NS)constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles(IONPs)and icaritin(ICA).Four types of nano-scaffolds(NS,ICA@NS,NS-IONPs and ICA@NS-IONPs)were prepared.The incorporation of ICA and IONPs minimally impact their surface morphological and chemical properties.IONPs enhanced the mechanical properties of NS scaffolds,including hardness,tensile strength,and elastic modulus.In vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase(ALP)activity level,expressions of osteogenesis-related genes and proteins as well as mineralized nodule formation.Mechanistic investigations revealed that MEK/ERK(MAP kinase-ERK kinase(MEK)/extracellularsignal-regulated kinase(ERK))signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@NS-IONPs.Furthermore,the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone regeneration.Therefore,IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.

Current applications and future prospects of nanotechnology in cancer immunotherapy

Cancer immunotherapy is an artificial stimulation of the immune system to recognize cancer cells and activate specific immune cells to target and attack cancer cells.In clinical trials, immunotherapy has recently shown impressive results in the treatment of multiple cancers.Thus, cancer immunotherapy has gained a lot of attention for its unique advantages and promising future.With extensive research on cancer immunotherapy, its safety and effectiveness has gradually been revealed.However, it is still a huge challenge to expand and drive this therapy while maintaining low toxicity, high specificity, and long-lasting efficacy.As a unique technology, nanotechnology has been applied in many fields, the advantages of which will promote the development of cancer immunotherapies.Researchers have tried to apply nanomaterials to cancer immunotherapy due to their advantageous properties,such as large specific surface areas, effective drug delivery, and controlled surface chemistry, to improve treatment efficacy.Here,we briefly introduce the current applications of nanomaterials in cancer immunotherapy, including adoptive cell therapy(ACT),therapeutic cancer vaccines, and monoclonal antibodies, and throw light on future directions of nanotechnology-based cancer immunotherapy.

Review: Progress in the Preparation of Iron Based Magnetic Nanoparticles for Biomedical Applications

With unique physical properties, chemical properties, and biological effects, magnetic nanomaterials are important functional materials in many fields. In the past decades, iron based magnetic nanomaterials have attracted much attention in the biomedicine field due to their superior magnetic properties and great potential in biomedical applications. In particular, magnetic iron oxide nanoparticles(MIONPs) have been playing a crucial role in the biomedicine field because of their diagnostic and therapeutic functions. Meanwhile, MIONPs are benign, low toxic, biocompatible, and biodegradable, so they are the only inorganic magnetic nanomaterials approved by the U.S. Food and Drug Administration(FDA) for clinical use at present. In this review, we mainly introduce the progress in the preparation of iron based magnetic nanomaterials for biomedical applications, including pure iron nanoparticles, iron-based alloy nanoparticles, and MIONPs, with a focus on MIONPs. Also, we summarize the preparation methods of MIONPs and point out the importance of their developments.

γ⁃Fe2O3@carboxymethyl Cellulose as Potential Oral Nanomedicine for Iron Deficiency Anemia Treatment on Rats

Oral iron supplements such as ferrous iron salts are major treatment agents for iron deficiency anemia(IDA)due to the convenience of large dose administration and good patient compliance.However,the gastrointestinal adverse impact caused by Fe2+stimulus and low bioavailability severely impedes its therapeutic effects.In recent years,it has been found that nano iron⁃based nanoparticles with high surface⁃to⁃volume ratio and low iron ion leakage can alleviate the toxic effect and improve the gastrointestinal absorbance.For further clinical development,nano materials need to meet the pharmaceutical quality demand.Carboxymethyl cellulose(CMC)is a significant pharmaceutical ingredient applied in approved drug formulations,and polyglucosorbitol carboxymethylether(PSC)has been utilized in iron⁃based nanomedicine ferumoxytol synthesis,both of which can be firmly anchored on iron oxide by carboxyl chelation.In this work,iron oxide nanoparticles(NPs)modified with CMC were designed and synthesized,and the structure composition and physicochemical properties were distinctly characterized.Oral supplement effects on rat IDA were investigated and compared with other recently reported iron supplements including NPs modified with PSC.Results show that the oral nano iron supplement achieved the recovery of hemoglobin and serum iron level in only two weeks with high safety.The nano iron oxide modified with pharmaceutical excipients provides new potential approach for oral iron supplement available in clinics.

Amperometric glucose biosensor based on gold nanorods and chitosan comodified Au electrode

Au nanorods were prepared by a seeding growth approach and used in fabricating the nanorod-enhancing glucose biosensor. The high affinity of chitosan for Au nanorods associated with its amino groups resulted in the formation of a layer of Au nanorods on the surface of Au electrode. It served as an intermediator to retain high efficient and stable immobilization of the enzyme. The performance of biosensors was investigated by cyclic voltammetry （CV）, in the presence of artificial redox mediator, ferrocenecarboxaldehyde. The biosensor had a fast response to glucose, and the response time was less than 10 s. The results indicated that the gold nanorods could enhance the current response to glucose. The detection limits of glucose can reach 10 mM, and the Michaelis-Menten constant Km^app is 13.62 mM.

In situ nanobubble sizing by visualization particle tracking and image-based dynamic light scattering

A novel method combining visualization particle tracking with image-based dynamic light scattering was developed to achieve the in situ and real-time size measurement of nanobubbles(NBs).First,the in situ size distribution of NBs was visualized by dark-field microscopy.Then,real-time size during the preparation was measured using image-based dynamic light scattering,and the longitudinal size distribution of NBs in the sample cell was obtained in a steady state.Results show that this strategy can provide a detailed and accurate size of bubbles in the whole sample compared with the commercial ZetaSizer Nano equipment.Therefore,the developed method is a real-time and simple technology with excellent accuracy,providing new insights into the accurate measurement of the size distribution of NBs or nanoparticles in solution.

An image analysis method for quantification of hepatic perfusion based on contrast-enhanced ultrasound imaging

Information about hepatic perfusion is used in clinical liver disease diagnosis. An image analy-sis system can help physicians make efficient and accurate diagnosis. The objective of this study is to propose an image analysis method for the quantification of the hepatic perfusion based on contrast-enhanced ultrasound imaging (CEUI). The proposed method contains frame selection, image registration, digital subtraction and grey-scale calculation. Then, by processing an image sequence, a time-intensity curve (TIC) for hepatic perfusion is derived. The kernel of this image analysis technology is digital subtrac-tion and its accuracy is improved by frame selec-tion and image registration. The advantage of this method is that it can obtain the perfusion information of the whole liver which is rarely ob-tained by traditional image analysis technology;therefore, it is a supplement of the traditional image analysis method. This method is applied on the quantification of a rabbit’s hepatic perfu-sion and the result shows the efficiency of it.

Synthesis of a novel functional group-bridged magnetized bentonite adsorbent:Characterization,kinetics,isotherm,thermodynamics and regeneration

A novel magnetic adsorbent was synthesized by magnetizing bentonite by APTES-Fe_3O_4 via a functional groupbridged interaction. The characterization of APTES-Fe_3O_4/bentonite was conducted via transmission electron microscope(TEM), X-ray diffraction(XRD), Fourier transform infrared spectrophotometer(FT-IR), thermal gravimetric analysis(TGA), vibrating sample magnetometer(VSM), zeta potential analysis and Brunner–Emmet–Teller(BET). The APTES-Fe_3O_4/bentonite was assessed as adsorbents for methylene blue(MB) with a high adsorption capacity(91.83 mg·g^(-1)). Factors affecting the adsorption of MB(such as p H, equilibrium time, temperature and initial concentration) were investigated. The adsorption process completely reaches equilibrium after 120 min and the maximum sorption is achieved at p H 8.0. The adsorption trend follows the pseudosecond order kinetics model. The adsorption data gives good fits with Langmuir isotherm model. The parameter factor RLfalls between 0 and 1, indicating the adsorption of MB is favorable. The adsorption process is endothermic with positive ΔH^0 values. The positive values of ΔG^0 confirm the affinity of the adsorbent towards MB, and suggest an increased randomness at the solid–liquid interface during the adsorption process. Regeneration of the saturated adsorbent was easily carried out via gamma-irradiation.

Preparation of Intelligent Supramolecular Hydrogels and Its application as 3D culture scaffold of ovarian cancer cell

Destination:to prepare intelligent suparmolecular hydrogel by mimicking the key features of extracellular matrices(ECM)and culture ovarian cancer cells in 3D mold,then investigate the influence of microenvironments on behavior of cells.Method:Through using the inclusion complexes interact between trans-azobenzene(or adaman-

Reactive oxygen species(ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery

Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis;however,the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells.Here,we report reactive oxygen species(ROS)-responsive and size-reducible nanoassemblies,formed by multivalent host-guest interactions betweenβ-cyclodextrins(β-CD)-anchored discoidal recombinant high-density lipoprotein(NP^(3)_(ST))and hyaluronic acid-ferrocene(HA-Fc)conjugates.The HA-Fc/NP^(3)_(ST)nanoassemblies have extended blood circulation time,specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium,rapidly disassemble in response to excess ROS in the intimal and release smaller NP^(3)_(ST),allowing for further plaque penetration,macrophage-targeted cholesterol efflux and drug delivery.In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP^(3)_(ST)reduces plaque size by 53%,plaque lipid deposition by 63%,plaque macrophage content by 62%and local inflammatory factor level by 64%compared to the saline group.Meanwhile,HA-Fc/NP^(3)_(ST)alleviates systemic inflammation characterized by reduced serum inflammatory factor levels.Collectively,HA-Fc/NP^(3)_(ST)nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability,thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.

Iron oxide nanoparticles:A promising approach for diagnosis and treatment of cardiovascular diseases

Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases(CVDs),it remains a leading cause of mortality and morbidity worldwide.This underscores the urgency for innovative approaches aiming at early and precise detection and treatment of CVDs to reduce the disease burden.Iron oxide nanoparticles(IONPs),with their unique magnetism and bioproperties,have shown great potential in this regard.In this review,we will begin with a brief overview of the synthesis and properties of IONPs.We will then focus on the latest applications of IONPs in CVDs,including diagnosis and treatment.The use of IONPs in the integration of diagnosis and treatment for CVDs is a promising field,and will be addressed in a separate section.The translational potential and challenges of IONPs will also be discussed.In conclusion,ongoing research and development of IONP-based strategies are highly likely to address current challenges effectively,and offer more personalized and efficient options for the diagnosis and treatment of CVDs.

Ag nanoparticles sensitize IR-induced killing of cancer cells

Dear Editor, Nanosized particulate systems combining better cancer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques. The surface of these nanoscale carriers is often functionalized with biological molecules for stabilization and targeted delivery. The combinations of nano-core and associated functional molecules can cross the cell membrane [1], and the surface of nanomaterials （including coating and associated functional molecules） plays a critical role in determining the outcome of their interactions with cells [2, 3]. Studying the potential effects of nanomaterials in biological systems often requires the administration of nanoparticles into a cell culture system or into living organisms in vivo. It should be noted, however, that under such conditions nanopaticles are known to adsorb proteins from the biological system,

Size-dependent peroxidase-like catalytic activity of Fe_3O_4 nanoparticles

Peroxidase-like catalytic properties of Fe3O4 nanoparficles （NPs） with three different sizes, synthesized by chemical coprecipitation and sol-gel methods, were investigated by UV-vis spectrum analysis. By comparing Fe3O4 NPs with average diameters of 11, 20, and 150 nm, we found that the catalytic activity increases with the reduced nanoparticle size. The electrochemical method to characterize the catalytic activity of Fe3O4 NPs using the response currents of the reaction product and substrate was also developed.

An all-silk-derived functional nanosphere matrix for sequential biomolecule delivery and in situ osteochondral regeneration

Endogenous repair of osteochondral defect is usually limited by the insufficient number of cells in the early stage and incomplete cell differentiation in the later stage.The development of drug delivery systems for sequential release of pro-migratory and pro-chondrogenic molecules to induce endogenous bone marrow-derived mesenchymal stem cells(BMSCs)recruitment and chondrogenic differentiation is highly desirable for in situ osteochondral regeneration.In this study,a novel,all-silk-derived sequential delivery system was fabricated by incorporating the tunable drug-loaded silk fibroin(SF)nanospheres into a SF porous matrix.The loading efficiency and release kinetics of biomolecules depended on the initial SF/polyvinyl alcohol(PVA)concentrations(0.2%,1%and 5%)of the nanospheres,as well as the hydrophobicity of the loaded molecules,resulting in controllable and programmed delivery profiles.Our findings indicated that the 5%nanosphere-incorporated matrix showed a rapid release of E7 peptide during the first 120 h,whereas the 0.2%nanosphere-incorporated matrix provided a slow and sustained release of Kartogenin(KGN)longer than 30 days.During in vitro culture of BMSCs,this functional SF matrix incorporated with E7/KGN nanospheres showed good biocompatibility,as well as enhanced BMSCs migration and chondrogenic differentiation through the release of E7 and KGN.Furthermore,when implanted into rabbit osteochondral defect,the SF nanosphere matrix with sequential E7/KGN release promoted the regeneration of both cartilage and subchondral bone.This work not only provided a novel all-silk-derived drug delivery system for sequential release of molecules,but also a functional tissueengineered scaffold for osteochondral regeneration.

Transmission electron microscopy and atomic force microscopy characterization of nickel deposition on bacterial cells

Recently bacterial cells have become attractive biological templates for the fabrication of metal nano- structures or nanomaterials due to their inherent small size, various standard geometrical shapes and abundant source. In this paper, nickel-coated bacterial cells (gram-negative bacteria of Escherichia coli) were fabricated via electroless chemical plating. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) characterization results reveal evident morphological difference between bacterial cells before and after deposition with nickel. The bare cells with smooth surface presented transverse outspreading effect at mica surface. Great changes took place in surface roughness for those bacterial cells after metallization. A large number of nickel nanoparticles were observed to be equably distributed at bacterial surface after activation and subsequent metallization. Furthermore, ultra thin section analytic results validated the presence and uniformity of thin nickel coating at bacte- rial surface after metallization.

Calculated Optical Properties of Dielectric Shell Coated Gold Nanorods

Optical absorption spectra of dielectric shell coated gold nanorods are simulated using the discrete dipole ap- proximation method. The influence of the aspect ratio, shell thickness, dielectric constant of the shell, and surrounding medium on the longitudinal resonance mode is investigated. It is found that the coated dielectric shell does not affect the trend in the dependence of resonance position on the aspect ratio, while it broadens the resonant line width and reduces the sensitivity of plasmon resonance in response to changes of the surrounding medium. F^arthermore, the difference of dielectric constants between the shell and surrounding medium plays an important role in determining the resonance position. The screening effect of the dielectric shell tends to be less apparent for a thicker shell thickness.Optical absorption spectra of dielectric shell coated gold nanorods are simulated using the discrete dipole ap- proximation method. The influence of the aspect ratio, shell thickness, dielectric constant of the shell, and surrounding medium on the longitudinal resonance mode is investigated. It is found that the coated dielectric shell does not affect the trend in the dependence of resonance position on the aspect ratio, while it broadens the resonant line width and reduces the sensitivity of plasmon resonance in response to changes of the surrounding medium. F^urthermore, the difference of dielectric constants between the shell and surrounding medium plays an important role in determining the resonance position. The screening effect of the dielectric shell tends to be less apparent for a thicker shell thickness.

Ultrathin FeS nanosheets with high chemodynamic activity for sensitive colorimetric detection of H_(2)O_(2) and glutathione

Iron chalcogenides have attracted great interest as potential substitutes of nature enzymes in the colorimetric biological sensing due to their unique chemodynamic characteristics.Herein,we report the preparation of ultrathin Fe S nanosheets(NSs)by a simple one-pot hydrothermal method and the prepared Fe S NSs exhibit strong Fenton-reaction activity to catalyze hydrogen peroxide(H_(2)O_(2))for generation of hydroxyl radical(^(·)OH).Based on the chromogenic reaction of resultant^(·)OH with 3,3,5,5-tetramethylbenzidine(TMB),we develop colorimetric biosensors for highly sensitive detection of H_(2)O_(2)and glutathione(GSH).The fabricated biosensors show wide linear ranges for the detection of H_(2)O_(2)(5–150μmol/L)and GSH(5–50μmol/L).Their detection limits for H_(2)O_(2)and GSH reach as low as0.19μmol/L and 0.14μmol/L,respectively.The experimental results of sensing intracellular H_(2)O_(2)and GSH demonstrate that this colorimetric method can realize the accurate detection of H_(2)O_(2)and GSH in normal cells(L02 and 3T3)and cancer cells(MCF-7 and He La).Our results have demonstrated that the synthesized Fe S NSs is a promising material to construct colorimetric biosensors for the sensitive detection of H_(2)O_(2)and GSH,holding great promising for medical diagnosis in cancer therapy.

Superparamagnetic iron oxide nanoparticles assembled magnetic nanobubbles and their application for neural stem cells labeling

Micro/nanobubbles for use as ultrasound contrast agents have been fabricated with different shell materials.When various biomedical nanoparticles have been embedded in the shells of bubbles,the composite structures have shown promising applications in multi-modal imaging,drug/gene delivery,and biomedical sensing.In this study,we developed a new gas-liquid interface self-assembly method to prepare magnetic nanobubbles embedded with superparamagnetic iron oxide nanoparticles(SPIONs).The diameter of the generated assembled nanobubbles was 227.40±87.21 nm with a good polydispersity index(PDI)of 0.29.Under the condition of 150 compression cycles,the nanobubble concentration could reach about 6.12×10^(9)/mL.Transmission electron microscopy(TEM)and scanning electronic microscopy(SEM)demonstrated that the assembled nanobubbles had a hollow gas core with SPIONs adsorbed on the surface.Ultrasound(US)imaging and magnetic resonance imaging(MRI)experiments indicated that the assembled magnetic nanobubbles exhibited good US and MR contrast capabilities.Moreover,the assembled magnetic nanobubbles were used to label neural stem cells under ultrasound exposure.After 40 s US exposure,the magnetic nanobubbles could be delivered into cells with 2.80 pg Fe per cell,which could be observed in the intracellular endosome by TEM.Compared with common incubation methods,the ultrasound exposure method did not introduce the potential cytotoxicity of transfection reagents and the efficiency was about twice as high as the efficiency of incubation.Therefore,the assembled magnetic nanobubbles prepared through the pressure-driven gas-liquid interface assembly approach could be a potential US/MRI dual model imaging nanocarrier for regenerative applications.