Surface modified superparamagnetic nanoparticles for drug delivery: Interaction studies with human fibroblasts in culture

The concept of drug delivery using magnetic nanoparticles greatly benefit from the fact that nanotechnology has developed to a stage that it makes possible not only to produce magnetic nanoparticles in a very narrow size distribution range with superparamagnetic properties but also to engineer particle surfaces to provide site specific delivery of drugs. The size and surface characteristics of the nanoparticles are crucial factors that determine the success of the particles when used in vivo. The aim of this study was to modify the surfaces of the magnetic nanoparticles with PEG to improve the biocompatibility of the nanoparticles by resisting protein adsorption and increasing their intracellular uptake. In this study, the poly(ethyleneglycol) (PEG) modified superparamagnetic iron oxide nanoparticles have been prepared and their influence on human dermal fibroblasts is assessed in terms of cell adhesion/viability, morphology, particle uptake and cytoskeletal organisation studies. Various techniques have been used to determine nanoparticle-cell interactions including light, fluorescence, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The modification of nanoparticle surface induced alterations in cell behaviour distinct from the unmodified particles, suggesting that cell response can be directed via specifically engineered particle surfaces.     

Fluorescent Magnetic Fe3O4/Rare Earth Colloidal Nanoparticles for Dual‐Modality Imaging

Fluorescent magnetic colloidal nanoparticles (FMCNPs) are produced by a two‐step, seed emulsifier‐free emulsion polymerization in the presence of oleic acid and sodium undecylenate‐modified Fe₃O₄ nanoparticles (NPs). The Fe₃O₄/poly(St‐co‐GMA) nanoparticles are first synthesized as the seed and Eu(AA)₃Phen is copolymerized with the remaining St and GMA to form the fluorescent polymer shell in the second step. The uniform core–shell structured FMCNPs with a mean diameter of 120 nm exhibit superparamagnetism with saturation magnetization of 1.92 emu/g. Red luminescence from the FMCNPs is confirmed by the salient fluorescence emission peaks of europium ions at 594 and 619 nm as well as 2‐photon confocal scanning laser microscopy. The in vitro cytotoxicity test conducted using the MTT assay shows good cytocompatibility and the T₂ relaxivity of the FMCNPs is 353.86 mM^?1S^?1 suggesting its potential in magnetic resonance imaging (MRI). In vivo MRI studies based on a rat model show significantly enhanced T₂‐weighted images of the liver after administration and prussian blue staining of the liver tissue slice reveals accumulation of FMCNPs in the organ. The cytocompatibility, superparamagnetism, and excellent fluorescent properties of FMCNPs make them suitable for biological imaging probes in MRI and optical imaging.     

One-pot synthesis of AuPt alloyed nanoparticles by intense x-ray irradiation

We synthesized AuPt alloyed nanoparticles in colloidal solution by a one-pot procedure based on synchrotron x-ray irradiation in the presence of PEG (polyethylene glycol). The exclusive presence of alloyed nanoparticles with fcc structure was confirmed by several different experiments including UV-vis spectroscopy, x-ray diffraction (XRD) and transmission electron microscopy (TEM). The composition of the AuPt alloyed nanoparticles can be varied in a continuous fashion by simply varying the feed ratios of Au and Pt precursors. The nanoparticles exhibited colloidal stability and biocompatibility, important for potential applications.     

常压辉光放电等离子体制备荧光碳纳米粒子

采用常压辉光放电等离子体制备了超细荧光碳纳米粒子。分别采用聚乙二醇(PEG)2000和聚乙烯吡咯烷酮(PVP)20000作为表面活性剂和表面修饰剂,利用辉光放电等离子体射流产生的大量高能电子等活性粒子分解乙醇溶液制备碳纳米粒子。采用透射电子显微镜和荧光分光光度计对生成物的形貌和荧光特性进行了检测。结果表明,生成物为石墨相的荧光碳纳米颗粒。随着反应时间的延长,生成物的荧光强度增强;采用PEG-2000修饰后产物的荧光强度比采用PVP-20000更强;丝状放电模式下生成物的荧光强度高于辉光放电模式。制备的碳纳米颗粒的荧光量子产率为46.58%。     

Labeling TiO2 Nanoparticles with Dyes for Optical Fluorescence Microscopy and Determination of TiO2–DNA Nanoconjugate Stability

Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO₂) nanoparticles. These nanoparticles, when electronically linked to single‐stranded DNA oligonucleotides, have been proposed to be used both as gene knockout devices and as possible tumor imaging agents. By interacting with complementary target sequences in living cells, these photoinducible TiO₂–DNA nanoconjugates have the potential to cleave intracellular genomic DNA in a sequence specific and inducible manner. The nanoconjugates also become detectable by magnetic resonance imaging with the addition of gadolinium Gd(III) contrast agents. Herein two approaches for labeling TiO₂ nanoparticles and TiO₂–DNA nanoconjugates with optically fluorescent agents are described. This permits direct quantification of fluorescently labeled TiO₂ nanoparticle uptake in a large population of living cells (>10⁴ cells). X‐ray fluorescence microscopy (XFM) is combined with fluorescent microscopy to determine the relative intracellular stability of the nanoconjugates and used to quantify intracellular nanoparticles. Imaging the DNA component of the TiO₂–DNA nanoconjugate by fluorescent confocal microscopy within the same cell shows an overlap with the titanium signal as mapped by XFM. This strongly implies the intracellular integrity of the TiO₂–DNA nanoconjugates in malignant cells.     

One-pot synthesis of near-infrared fluorescent gold clusters for cellular fluorescence lifetime imaging

A facile strategy to synthesize water-soluble fluorescent gold nanoclusters (Au NCs) stabilized with the bidentate ligand dihydrolipoic acid (DHLA) is reported. The DHLA-capped Au NCs are characterized by UV-vis absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. The Au NCs possess many attractive features including ultrasmall size, bright near-infrared luminescence, high colloidal stability, and good biocompatibility, making them promising imaging agents for biomedical and cellular imaging applications. Moreover, their long fluorescence lifetime (>100 ns) makes them attractive as labels in fluorescence lifetime imaging (FLIM) applications. As an example, the internalization of Au NCs by live HeLa cells is visualized using the FLIM technique.     

Photosensitizer‐Conjugated Albumin−Polypyrrole Nanoparticles for Imaging‐Guided In Vivo Photodynamic/Photothermal Therapy

Conjugated polymers with strong absorbance in the near‐infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA‐Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd³⁺, Ce6 in PPy@BSA‐Ce6 nanoparticles after being labeled with Gd³⁺ enables dual‐modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor‐bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA‐Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one‐step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented.     

Synthesis and characterization of CdTe quantum dots embedded gelatin nanoparticles via a two-step desolvation method

Novel CdTe quantum dots (QDs) embedded gelatin nanoparticles (CdTe/gelatin nanoparticles) were synthesized via a two-step desolvation method. The morphology and size distribution of the nanoparticles were characterized by transmission electron microscope (TEM) and laser particle size analyzer. They are presented spherically and relatively uniform with a diameter of 150 nm. The luminescent properties of the nanoparticles were investigated by using fluorescence spectrophotometry and fluorescence microscopy. The fluorescence stability of nanoparticles was tested in vitro. It was found that the nanoparticles were stable in water and phosphate-buffered saline (PBS) solution (pH 7.4) for at least 15 days. A possible formation mechanism of the CdTe/gelatin nanoparticles was also proposed. The inherent stability and biocompatibility indicate that the nanoparticles are expected to be promising candidates for in vivo biological imaging studies.     

A biocompatible approach to surface modification: Biodegradable polymer functionalized super-paramagnetic iron oxide nanoparticles

In the study, Fe₃O₄ nanoparticles with a size range of 10–20 nm were firstly prepared by the modified controlled chemical coprecipitation method from the solution of ferrous/ferric mixed salt-solution in alkaline medium. Then, the super-paramagnetic iron oxide nanoparticles were covalently modified by biodegradable polymers such as polyethylene glycol (PEG) and poly(ethylene glycol)-co-poly(d,l-lactide) (PELA). The size and its distribution of the nanoparticles were determined by dynamic light scattering measurements (DLS). The magnetic nanoparticles was characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), electron diffraction (ED), Fourier transform infrared spectroscopy (FT-IR) and UV–visible spectrophotometry (UV). Magnetic properties were measured using a vibrating sample magnetometer. And the 5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the biocompatibility of the magnetic nanoparticles. The results showed that the Fe₃O₄ nanoparticles functionalized by PEG and PELA possessed a mean size of 43.2 and 79.3 nm, respectively, and exhibited an excellent biocompatibility.     

Multifunctional Upconversion Mesoporous Silica Nanostructures for Dual Modal Imaging and In Vivo Drug Delivery

Incorporating the agents for magnetic resonance imaging (MRI), optical imaging, and therapy in one nanostructured matrix to construct multifunctional nanomedical platform has attracted great attention for simultaneous diagnostic and therapeutic applications. In this work, a facile methodology is developed to construct a multifunctional anticancer drug nanocarrier by combining the special advantages of upconversion nanoparticles and mesoporous silica. β‐NaYF₄:Yb³⁺, Er³⁺@β‐NaGdF₄:Yb³⁺ is chosen as it can provide the dual modality of upconversion luminescence and MRI. Then mesoporous silica is directly coated onto the upconversion nanoparticles to form discrete, monodisperse, highly uniform, and core–shell structured nanospheres (labeled as UCNPs@mSiO₂), which are subsequently functionalized with hydrophilic polymer poly(ethylene glycol) (PEG) to improve the colloidal stability and biocompatibility. The obtained multifunctional nanocomposites can be used as an anticancer drug delivery carrier and applied for imaging. The anticancer drug doxorubicin (DOX) is absorbed into UCNPs@mSiO₂‐PEG nanospheres and released in a pH‐sensitive pattern. In vitro cell cytotoxicity tests on cancer cells verify that the DOX‐loaded UCNPs@mSiO₂‐PEG has comparable cytotoxicity with free DOX at the same concentration of DOX. In addition, the T₁‐weighted MRI that measures in aqueous solutions reveals that the contrast brightening increases with the concentration of Gd³⁺ component. Upconversion luminescence images of UCNPs@mSiO₂‐PEG uptaken by cells show green emission under 980 nm infrared laser excitation. Finally, the nanocomposites show low systematic toxicity and high in vivo antitumor therapy efficacy. These findings highlight the fascinating features of upconversion‐mesoporous nanocomposites as multimodality imaging contrast agents and nanocarrier for drug molecules.     

Nickel oxide/polypyrrole/silver nanocomposites with core/shell/shell structure: Synthesis,characterization and their electrochemical behaviour with antimicrobial activities

Magnetic and conducting Nickel oxide–polypyrrole (NiO/PPy) nanoparticles with core–shell structure were prepared in the presence of Nickel oxide (NiO) in aqueous solution containing sodium dodecyl benzenesulfonate (SDBS) as a surfactant as well as dopant. A stable dispersion of silver (Ag) nanoparticles was synthesized by chemical (citrate reduction) method. NiO/PPy nanocomposites were added to the Ag colloid under stirring. Ag nanoparticles could be electrostatically attracted on the surface of NiO/PPy nanocomposites, leading to formation of NiO/PPy/Ag nanocomposites with core/shell/shell structure. The morphology, structure, particle size and composition of the products were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, cyclic voltammetry (CV) and current–voltage (I–V) analysis. The resultant nanocomposites have the good conductivity and excellent electrochemical and catalytic properties of PPy and Ag nanoparticles. Furthermore, the nanocomposites showed excellent antibacterial behaviour due to the presence of Ag nanoparticles in the composite. The thermal stability of NiO–PPy as well as NiO/PPy/Ag nanocomposites was higher than that of pristine PPy. Studies of IR spectra suggest that the increased thermal stability may be due to interactions between NiO and Ag nanoparticles with the PPy backbone.     

Fluorescence‐Encoded Gold Nanoparticles: Library Design and Modulation of Cellular Uptake into Dendritic Cells

In order to harness the unique properties of nanoparticles for novel clinical applications and to modulate their uptake into specific immune cells we designed a new library of homo‐ and hetero‐functional fluorescence‐encoded gold nanoparticles (Au‐NPs) using different poly(vinyl alcohol) and poly(ethylene glycol)‐based polymers for particle coating and stabilization. The encoded particles were fully characterized by UV‐Vis and fluorescence spectroscopy, zeta potential and dynamic light scattering. The uptake by human monocyte derived dendritic cells in vitro was studied by confocal laser scanning microscopy and quantified by fluorescence‐activated cell sorting and inductively coupled plasma atomic emission spectroscopy. We show how the chemical modification of particle surfaces, for instance by attaching fluorescent dyes, can conceal fundamental particle properties and modulate cellular uptake. In order to mask the influence of fluorescent dyes on cellular uptake while still exploiting its fluorescence for detection, we have created hetero‐functionalized Au‐NPs, which again show typical particle dependent cellular interactions. Our study clearly prove that the thorough characterization of nanoparticles at each modification step in the engineering process is absolutely essential and that it can be necessary to make substantial adjustments of the particles in order to obtain reliable cellular uptake data, which truly reflects particle properties.     

Colloidally Stable Silicon Nanocrystals with Near‐Infrared Photoluminescence for Biological Fluorescence Imaging

Luminescent silicon nanocrystals (ncSi) are showing great promise as photoluminescent tags for biological fluorescence imaging, with size‐dependent emission that can be tuned into the near‐infrared biological window and reported lack of toxicity. Here, colloidally stable ncSi with NIR photoluminescence are synthesized from (HSiO_1.5)_n sol–gel glasses and are used in biological fluorescence imaging. Modifications to the thermal processing conditions of (HSiO_1.5)_n sol–gel glasses, the development of new ncSi oxide liberation chemistry, and an appropriate alkyl surface passivation scheme lead to the formation of colloidally stable ncSi with photoluminescence centered at 955 nm. Water solubility and biocompatibility are achieved through encapsulation of the hydrophobic alkyl‐capped ncSi within PEG‐terminated solid lipid nanoparticles. Their applicability to biological imaging is demonstrated with the in‐vitro fluorescence labelling of human breast tumor cells.     

The Nanoassembly of an Intrinsically Cytotoxic Near‐Infrared Dye for Multifunctionally Synergistic Theranostics

The combination of diagnostic and therapeutic functions in a single theranostic nanoagent generally requires the integration of multi‐ingredients. Herein, a cytotoxic near‐infrared (NIR) dye (IR‐797) and its nanoassembly are reported for multifunctional cancer theranostics. The hydrophobic IR‐797 molecules are self‐assembled into nanoparticles, which are further modified with an amphiphilic polymer (C18PMH‐PEG5000) on the surface. The prepared PEG‐IR‐797 nanoparticles (PEG‐IR‐797 NPs) possess inherent cytotoxicity from the IR‐797 dye and work as a chemotherapeutic drug which induces apoptosis of cancer cells. The IR‐797 NPs are found to have an ultrahigh mass extinction coefficient (444.3 L g^?1 cm^?1 at 797 nm and 385.9 L g^?1 cm^?1 at 808 nm) beyond all reported organic nanomaterials (<40 L g^?1 cm^?1) for superior photothermal therapy (PTT). In addition, IR‐797 shows some aggregation‐induced‐emission (AIE) properties. Combining the merits of good NIR absorption, high photothermal energy conversion efficiency, and AIE, makes the PEG‐IR‐797 NPs useful for multimodal NIR AIE fluorescence, photoacoustic, and thermal imaging‐guided therapy. The research exhibits the possibility of using a single ingredient and entity to perform multimodal NIR fluorescence, photoacoustic, and thermal imaging‐guided chemo‐/photothermal combination therapy, which may trigger wide interest from the fields of nanomedicine and medicinal chemistry to explore multifunctional theranostic organic molecules.     

Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework‐Based Drug Delivery Systems

Endophthalmitis, derived from the infections of pathogens, is a common complication during the use of ophthalmology‐related biomaterials and after ophthalmic surgery. Herein, aiming at efficient photodynamic therapy (PDT) of bacterial infections and biofilm eradication of endophthalmitis, a pH‐responsive zeolitic imidazolate framework‐8‐polyacrylic acid (ZIF‐8‐PAA) material is constructed for bacterial infection–targeted delivery of ammonium methylbenzene blue (MB), a broad‐spectrum photosensitizer antibacterial agent. Polyacrylic acid (PAA) is incorporated into the system to achieve higher pH responsiveness and better drug loading capacity. MB‐loaded ZIF‐8‐PAA nanoparticles are modified with AgNO₃/dopamine for in situ reduction of AgNO₃ to silver nanoparticles (AgNPs), followed by a secondary modification with vancomycin/NH₂‐polyethylene glycol (Van/NH₂‐PEG), leading to the formation of a composite nanomaterial, ZIF‐8‐PAA‐MB@AgNPs@Van‐PEG. Dynamic light scattering, transmission electron microscopy, and UV–vis spectral analysis are used to explore the nanoparticles synthesis, drug loading and release, and related material properties. In terms of biological performance, in vitro antibacterial studies against three kinds of bacteria, i.e., Escherichia coli, Staphylococcus aureus, and methicillin‐resistant S. aureus, suggest an obvious superiority of PDT/AgNPs to any single strategy. Both in vitro retinal pigment epithelium cellular biocompatibility experiments and in vivo mice endophthalmitis models verify the biocompatibility and antibacterial function of the composite nanomaterials.     

Kinetic Study of the Formation of Polypyrrole Nanoparticles in Water‐Soluble Polymer/Metal Cation Systems: A Light‐Scattering Analysis

A facile way to synthesize nanometer‐sized polymer (polypyrrole, PPy) particles is explored on the basis of the formation of complexes between water‐soluble polymers and metal cations in aqueous solution. The metal cation is used as an oxidizing agent to initiate the chemical oxidation polymerization of the corresponding monomer, and the water‐soluble polymer effectively provides a steric stability for the growth of polymer nanoparticles during the polymerization process. Light‐scattering analyses are performed to give insight into the behavior of the complexes in aqueous solution. In addition, major physical parameters affecting the formation of polymer nanoparticles are investigated, including hydrodynamic radius, radius of gyration, shape factor, and viscosity. By judicious control of these parameters, PPy nanoparticles with narrow size distribution can be readily fabricated in large quantities. It is also possible to control the diameter of the nanoparticles by changing critical synthetic variables. Importantly, PPy nanoparticles of ≈ 20–60 nm in diameter can be prepared without using any surfactants or specific templates; this novel strategy offers great possibility for mass production of polymer nanoparticles.     

Iodine‐Rich Semiconducting Polymer Nanoparticles for CT/Fluorescence Dual‐Modal Imaging‐Guided Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) is a promising technique for cancer therapy, providing good therapeutic efficacy with minimized side effect. However, the lack of oxygen supply in the hypoxic tumor site obviously restricts the generation of singlet oxygen (¹O₂), thus limiting the efficacy of PDT. So far, the strategies to improve PDT efficacy usually rely on complicated nanosystems, which require sophisticated design or complex synthetic procedure. Herein, iodine‐rich semiconducting polymer nanoparticles (SPN‐I) for enhanced PDT, using iodine‐induced intermolecular heavy‐atom effect to elevate the ¹O₂ generation, are designed and prepared. The nanoparticles are composed of a near‐infrared (NIR) absorbing semiconducting polymer (PCPDTBT) serving as the photosensitizer and source of fluorescence signal, and an iodine‐grafted amphiphilic diblock copolymer (PEG‐PHEMA‐I) serving as the ¹O₂ generation enhancer and nanocarrier. Compared with SPN composed of PEG‐b‐PPG‐b‐PEG and PCPDTBT (SPN‐P), SPN‐I can enhance the ¹O₂ generation by 1.5‐fold. In addition, SPN‐I have high X‐ray attenuation coefficient because of the high density of iodine in PEG‐PHEMA‐I, providing SPN‐I the ability of use with computed tomography (CT) and fluorescence dual‐modal imaging. The study thus provides a simple nanotheranostic platform composed of two components for efficient CT/fluorescence dual‐modal imaging‐guided enhanced PDT.     

Dynamic light scattering and atomic force microscopy techniques for size determination of polyurethane nanoparticles

Nanoparticles have applications in various industrial fields principally in drug delivery. Nowadays, there are several processes for manufacturing colloidal polymeric systems and methods of preparation as well as of characterization. In this work, Dynamic Light Scattering and Atomic Force Microscopy techniques were used to characterize polyurethane nanoparticles. The nanoparticles were prepared by miniemulsion technique. The lipophilic monomers, isophorone diisocyanate (IPDI) and natural triol, were emulsified in water containing surfactant. In some formulations the poly(ethylene glycol) was used as co-monomer to obtain the hydrophilic and pegylated nanoparticles. Polyurethane nanoparticles observed by atomic force microscopy (AFM) were spherical with diameter around 209 nm for nanoparticles prepared without PEG. From AFM imaging two populations of nanoparticles were observed in the formulation prepared with PEG (218 and 127 nm) while dynamic light scattering (DLS) measurements showed a monodisperse size distribution around 250 nm of diameters for both formulations. The polydispersity index of the formulations and the experimental procedures could influence the particle size determination with these techniques.     

Preparations of bifunctional polymeric beads simultaneously incorporated with fluorescent quantum dots and magnetic nanocrystals

Bifunctional polystyrene beads simultaneously incorporated with fluorescent CdTe quantum dots (Q-dots) and superparamagnetic Fe(3)O(4) nanocrystals were prepared by a modified mini-emulsion polymerization method, in which polymerizable surfactants were used as both phase transfer agent for aqueous colloidal nanoparticles and emulsifier. In addition, silica coating was also introduced to Fe(3)O(4) nanocrystals for regulating the internal structure of the composite beads. Transmission electron microscopy, confocal fluorescence microscopy and conventional spectroscopy were used to characterize the composite beads, as well as the polymerizable surfactant-coated CdTe Q-dots and silica-coated Fe(3)O(4) nanoparticles. Different mixing methods were also attempted in order to vary the size of the resultant bifunctional beads.     

Chemically Tailoring Coal to Fluorescent Carbon Dots with Tuned Size and Their Capacity for Cu(II) Detection

The desired control of size, structure, and optical properties of fluorescent carbon dots (CDs) is critical for understanding the fluorescence mechanism and exploring their potential application. Herein, a top‐down strategy to chemically tailor the inexpensive coal to fluorescent CDs by a combined method of carbonization and acidic oxidation etching is reported. The size and optical properties of the as‐made CDs are tuned by controlling the structures of graphitic crystallites in the starting precursor. The coal‐derived CDs exhibit two different distinctive emission modes, where the intensity of the short‐wavelength emission is significantly enhanced by partial reduction treatment. The evolution of the electronic structure and the surface states analysis show that two different types of fluorescence centers, nano‐sized sp² carbon domains and surface defects, are responsible for the observed emission characteristics. The reduced CDs are demonstrated as an effective fluorescent sensing material for label‐free and selective detection of Cu(II) ions with a detection limit as low as 2.0 nm , showing a great promise for real‐world sensor applications.