Recent progress in biopolymer nanoparticle and microparticle formation by heat-treating electrostatic protein-polysaccharide complexes

Functional biopolymer nanoparticles or microparticles can be formed by heat treatment of globular protein-ionic polysaccharide electrostatic complexes under appropriate solution conditions. These biopolymer particles can be used as encapsulation and delivery systems, fat mimetics, lightening agents, or texture modifiers. This review highlights recent progress in the design and fabrication of biopolymer particles based on heating globular protein-ionic polysaccharide complexes above the thermal denaturation temperature of the proteins. The influence of biopolymer type, protein-polysaccharide ratio, pH, ionic strength, and thermal history on the characteristics of the biopolymer particles formed is reviewed. Our current understanding of the underlying physicochemical mechanisms of particle formation and properties is given. The information provided in this review should facilitate the rational design of biopolymer particles with specific physicochemical and functional attributes, as well as stimulate further research in identifying the physicochemical origin of particle formation.     

Reorganization of the structures,morphologies, and conformations of bulk polymers via coalescence from polymer–cyclodextrin inclusion compounds

Bulk poly(ethylene terephthalate) (PET) and bisphenol A polycarbonate (PC) samples have been produced by the coalescence of their segregated, extended chains from the narrow channels of the crystalline inclusion compounds (ICs) formed between the γ‐cyclodextrin (CD) host and PET and PC guests, which are reported for the first time. Differential scanning calorimetry, Fourier transform infrared, and X‐ray observations of PET and PC samples coalesced from their crystalline γ‐CD‐ICs suggest structures and morphologies that are different from those of samples obtained by ordinary solution and melt processing techniques. For example, as‐received PC is generally amorphous with a glass‐transition temperature (T_g) of about 150 °C; when cast from tetrahydrofuran solutions, PC is semicrystalline with a melting temperature (T_m) of about 230 °C; and after PC/γ‐CD‐IC is washed with hot water for the removal of the host γ‐CD and for the coalescence of the guest PC chains, it is semicrystalline but has an elevated T_m value of about 245 °C. PC crystals formed upon the coalescence of highly extended and segregated PC chains from the narrow channels in the γ‐CD host lattice are possibly more chain‐extended and certainly more stable than chain‐folded PC crystals grown from solution. Melting the PC crystals formed by coalescence from PC/γ‐CD‐IC produces a normal amorphous PC melt that, upon cooling, results in typical glassy PC. PET coalesced from its γ‐CD‐IC crystals, although also semicrystalline, displays a T_m value only marginally elevated from that of typical bulk or solution‐crystallized PET samples. However, after the melting of γ‐CD‐IC‐coalesced PET crystals, it is difficult to quench the resultant PET melt into the usual amorphous PET glass, characterized by a T_g value of about 80 °C. Instead, the coalesced PET melt rapidly recrystallizes during the attempted quench, and so upon reheating, it displays neither a T_g nor a crystallization exotherm but simply remelts at the as‐coalesced T_m. This behavior is unaffected by the coalesced PET sample being held above T_m for 2 h, indicating that the extended, unentangled nature of the chains in the noncrystalline regions of the coalesced PET are not easily converted into the completely disordered, randomly coiled, entangled melt. Apparently, the highly extended, unentangled characters of the PC and PET chains in their γ‐CD‐ICs are at least partially retained after they are coalesced. Initial differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared, and X‐ray observations are described here. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 992–1012, 2002     

Targeted Gastrointestinal Delivery of Nutraceuticals with Polysaccharide‐Based Coatings

Oral delivery is one of the facile methods for the administration of active ingredients (AIs) like nutraceuticals and drugs. However, its intrinsic disadvantages include poor absorption and bioavailability, degradation of the AI during transit through the gastrointestinal tract (GIT), and a lack of action specificity. Hence, a delivery system for targeted gastrointestinal delivery of AI using polysaccharide‐based polymers, that are generally recognized as safe and approved for use as a direct food additive, is proposed. In this regard, mucoadhesive chitosan nanoparticles that could adhere to the mucosa of the GIT are fabricated and encapsulated with AI. These particles are subsequently coated with polysaccharides that have different enzymatic susceptibilities, to allow for specific degradation in the small or large intestines. It is observed that the polysaccharide coating efficiently retarded the nonspecific release of the encapsulated agent until it is exposed to its intended environment of release. The cytotoxicity and uptake of chitosan nanoparticles is further evaluated on Caco2 cells. In conclusion, these polysaccharide‐coated nanoparticles can potentially be targeted to different organs in the GIT and to be taken up by the enterocytes for improved oral bioavailability.     

Non‐Covalent Polyvalent Ligands by Self‐Assembly of Small Glycodendrimers: A Novel Concept for the Inhibition of Polyvalent Carbohydrate–Protein Interactions In Vitro and In Vivo

Polyvalent carbohydrate–protein interactions occur frequently in biology, particularly in recognition events on cellular membranes. Collectively, they can be much stronger than corresponding monovalent interactions, rendering it difficult to control them with individual small molecules. Artificial macromolecules have been used as polyvalent ligands to inhibit polyvalent processes; however, both reproducible synthesis and appropriate characterization of such complex entities is demanding. Herein, we present an alternative concept avoiding conventional macromolecules. Small glycodendrimers which fulfill single molecule entity criteria self‐assemble to form non‐covalent nanoparticles. These particles—not the individual molecules—function as polyvalent ligands, efficiently inhibiting polyvalent processes both in vitro and in vivo. The synthesis and characterization of these glycodendrimers is described in detail. Furthermore, we report on the characterization of the non‐covalent nanoparticles formed and on their biological evaluation.     

Mechanical,thermal, and ultraviolet resistance properties of polycarbonate/cerium oxide composites

The composites containing polycarbonate (PC) and cerium oxide (CeO₂) nanoparticles as well as nanoparticles modified with stearic acid (mCeO₂) have been prepared using a melt blending method. The composites are studied by using FTIR spectroscopy, differential scanning calorimetry, thermal gravimetric analysis and scanning electron microscopy, and their tensile strength and ultraviolet (UV) resistance are examined. The results indicate that the introduction of CeO₂ nanoparticles at 1 wt% can improve the mechanical properties of PC, while a weight ratio that is over 1 wt% can lead to a reduction in the tensile strength. Compared with the PC/CeO₂ composites, the PC/mCeO₂ composites provide better mechanical properties. Besides, the introduction of CeO₂ nanoparticles gives PC promising UV resistance. However, different amounts of CeO₂ nanoparticles used provide similar thermal and UV resistance in PC. In a comparison of the PC/CeO₂ and PC/mCeO₂ composites, there are no apparent differences observed between CeO₂ and mCeO₂ on improving the UV resistance of PC.     

Emulsion stabilisation using polysaccharide–protein complexes

There is a great deal of interest in the Food Industry in the use of polysaccharides and proteins to stabilise oil-in-water emulsions and there is a particular interest nowadays in the use of polysaccharide–protein complexes. There are three classes of complexes namely; (a) naturally-occurring complexes in which protein residues are covalently attached to the polysaccharide chains as is the case, for example, with gum Arabic; (b) Maillard conjugates, which are formed by interaction of the reducing end of a polysaccharide with an amine group on a protein forming a covalent bond; and (c) electrostatic complexes formed between a polysaccharide and a protein with opposite net charge. This review sets out our current understanding of the nature of these different polysaccharide–protein complexes and their ability to stabilise oil-in-water emulsions.     

Silicone composites containing stabilized silver clusters or nanoparticles

Silver nanoparticles are of high importance due to their electrical, magnetic, and optical properties, as well as catalytic and biocidal activity that are superior to the bulk silver and other metals. To prepare certain devices, generally, silver is incorporated into a matrix either as preformed or in situ‐generated particles. Silver nanoparticles were generated in situ into a silicone matrix formed by cohydrolysis of the mixture of silanes, each of them having a certain role: dimethyldiethoxysilane (DMDES) as a precursor for highly flexible polydimethylsiloxane, methyltriethoxysilane (MTES) as a cross‐linker highly compatible with polydimethylsiloxane, and 3‐aminopropyltriethoxysilane as a stabilizer, since it can readily complex to silver atoms through its amine functionality. Dimethylformamide (DMF) was used as a solvent for the silver nitrate and reducing agent. The samples were investigated both in sol state and as aged coating films deposited on glass substrate. The complexation of the silver and the matrix formation were emphasized by FTIR. The size of the formed silicone particles encapsulating silver was estimated by dynamic light scattering (DLS) (about 100 nm) in sol and by AFM in film (about 90 nm). The formation of the clusters or nanoparticles depending on the ratio between the reducing and complexing agents was evidenced by UV–Vis absorption spectra. Thus, it would create conditions to stop and isolate clusters at the desired size by precise control of the experimental conditions. The composites could be used alone as antibacterial‐coating materials but also, porous silica having incorporated silver clusters with potential applicability in catalysis may result after their calcination. Copyright © 2010 John Wiley & Sons, Ltd.     

生化分析用荧光纳米粒子研究进展

荧光纳米粒子在生化分析领域的应用研究近十年来取得了令人瞩目的进展,引起了研究者的广泛关注,如何制备强荧光发光、高生物亲和的荧光纳米粒子是其在生化分析领域应用的前提和基础。本文评述了近年来在生化分析领域应用较多的几种荧光纳米粒子的研究进展与状况。引用文献103篇。     

The Vital Role of Buffer Anions in the Antioxidant Activity of CeO2 Nanoparticles

Cerium oxide (CeO₂) nanoparticles display excellent antioxidant properties by scavenging free radicals. However, some studies have indicated that they can cause an adverse response by generating reactive oxygen species (ROS). Hence, it is important to clarify the factors that affect the oxidant/antioxidant activities of CeO₂ nanoparticles. In this work, we report the effects of different buffer anions on the antioxidant activity of CeO₂ nanoparticles. Considering the main anions present in the body, Tris‐HCl, sulfate, and phosphate buffer solutions have been used to evaluate the antioxidant activity of CeO₂ nanoparticles by studying their DNA protective effect. The results show that CeO₂ nanoparticles can protect DNA from damage in Tris‐HCl and sulfate systems, but not in phosphate buffer solution (PBS) systems. The mechanism of action has been explored: cerium phosphate is formed on the surface of the nanoparticles, which interferes with the redox cycling between Ce³⁺ and Ce⁴⁺. As a result, the antioxidant activity of CeO₂ nanoparticles is greatly affected by the external environment, especially the anions. These results may provide guidance for the further practical application of CeO₂ nanoparticles.     

Platinum Nanoparticles: The Crucial Role of Crystal Face and Colloid Stabilizer in the Diastereoselective Hydrogenation of Cinchonidine

The preparation of stable metal nanoparticles requires a strong interaction between the (organic) stabilizer and the metal surface that might alter the catalytic properties. This behavior has been described as “poisoning” since the stabilizer normally decreases the catalytic activity due to site blocking. Here we show a striking influence of the stabilizer on the selectivity in the hydrogenation of cinchonidine (CD) over poly(acrylic acid) (PAA)‐stabilized Pt nanoparticles with well‐defined shape distributions. In the hydrogenation of the heteroaromatic ring of cinchonidine in toluene, the diastereomeric excess of the (S)‐hexahydrocinchonidine increased upon increasing Pt{111}/Pt{100} ratio, but this distinct shape selectivity was observed only after the oxidative removal of PAA at 473 K. The use of the as‐prepared nanoparticles inverted the major diastereomer to R, and this isomer was formed also in acetic acid. This striking change in the diastereoselectivity indicates that poly(acrylic acid), which remains on the Pt surface after preparation, interacts with CD during hydrogenation almost as strongly as the solvent acetic acid. The PAA stabilizer plays a dual role: it allows one to control the size and shape of the nanoparticles during their synthesis, and it affects the rate and diastereoselectivity of the hydrogenation of CD probably through a “surface‐localized acidification”.     

Hybrid Curdlan Poly(γ ‐Glutamic Acid) Nanoassembly for Immune Modulation in Macrophage

A nanoformulation composed of curdlan, a linear polysaccharide of 1,3‐β‐linked d ‐glucose units, hydrogen bonded to poly(γ ‐glutamic acid) (PGA), was developed to stimulate macrophage. Curdlan/PGA nanoparticles (C‐NP) are formulated by physically blending curdlan (0.2 mg mL^?1 in 0.4 m NaOH) with PGA (0.8 mg mL^?1). Forster resonance energy transfer (FRET) analysis demonstrates a heterospecies interpolymer complex formed between curdlan and PGA. The ¹H‐NMR spectra display significant peak broadening as well as downfield chemical shifts of the hydroxyl proton resonances of curdlan, indicating potential intermolecular hydrogen bonding interactions. In addition, the cross peaks in ¹H‐¹H 2D‐NOESY suggest intermolecular associations between the OH‐2/OH‐4 hydroxyl groups of curdlan and the carboxylic‐/amide‐groups of PGA via hydrogen bonding. Intracellular uptake of C‐NP occurs over time in human monocyte‐derived macrophage (MDM). Furthermore, C‐NP nanoparticles dose‐dependently increase gene expression for TNF‐α, IL‐6, and IL‐8 at 24 h in MDM. C‐NP nanoparticles also stimulate the release of IL‐lβ, MCP‐1, TNF‐α, IL‐8, IL‐12p70, IL‐17, IL‐18, and IL‐23 from MDM. Overall, this is the first demonstration of a simplistic nanoformulation formed by hydrogen bonding between curdlan and PGA that modulates cytokine gene expression and release of cytokines from MDM.     

基于生物大分子的纳米药物载体

生物大分子材料由于其可再生性、无毒性以及良好的生物相容性、生物可降解性和黏膜粘附性等特点成为药物载体研究的热点,尤其是将其作为纳米药物载体材料更加受人关注。本文首先对生物大分子纳米颗粒常用的制备方法--乳化法、自组装法和离子凝聚法进行了详细的介绍。由于乳化法在一定程度上破坏了生物大分子的生物相容性,因此自组装法和离子凝聚法是比较理想的制备方法。其中自组装法是利用两亲性的生物大分子,如蛋白质、多糖衍生物等在静电作用、疏水作用、范德华力等非键合作用力下组装成纳米结构;而离子凝聚法则是利用聚电解质与带相反电荷物质之间的静电作用形成纳米结构。接着本文对通过这些方法获得的生物大分子纳米颗粒作为蛋白类药物、抗癌药物以及基因药物的载体在近年来的研究进展进行了归纳和总结,结果显示其在药物缓释体系中具有广阔的应用前景。     

Oxidation‐Responsive Aliphatic Polycarbonates from N‐Substituted Eight‐Membered Cyclic Carbonate: Synthesis and Degradation Study

Oxidation‐responsive aliphatic polycarbonates represent a promising branch of functional biodegradable polymers. This paper reports the synthesis and ring‐opening polymerization (ROP) of an eight‐membered cyclic carbonate possessing phenylboronic pinacol ester ( C3 ) and the H₂O₂‐triggered degradation of its polymer ( PC3 ). C3 is prepared from the inexpensive and readily available diethanolamine with a moderate yield and undergoes the well‐controlled anionic ROP with a living character under catalysis of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene. It can also be copolymerized with l ‐lactide, trimethylene carbonate, and 5‐ter‐butyloxycarbonylamino trimethylene carbonate, affording the copolymers with a varied distribution of the repeating units. To clearly demonstrate the oxidative degradation mechanism of PC3 , this paper first investigates the H₂O₂‐induced decomposition of small‐molecule model compounds by proton nuclear magnetic resonance (¹H NMR). It is found that the adduct products formed by the in‐situ‐generated secondary amines and p‐quinone methide (QM) are thermodynamically unstable and can decompose slowly back to QM and the amines. On this basis, this paper further studies the H₂O₂‐accelerated degradation of PC3 nanoparticles that are prepared by the o/w emulsion method. A sequential process of oxidation of the phenylboronic ester, 1,6‐elimination of the in‐situ‐generated phenol, releasing CO₂ and intramolecular cyclization or isomerization is proposed as the degradation mechanism of PC3 .     

Injectable Nanohybrid Scaffold for Biopharmaceuticals Delivery and Soft Tissue Engineering

An injectable nanofibrous hydrogel scaffold integrated with growth factors (GFs) loaded polysaccharide nanoparticles was developed that specifically allows for targeted adipose‐derived stem cells (ASCs) encapsulation and soft tissue engineering. The nanofibrous hydrogel was produced via biological conjugation of biotin‐terminated star‐shaped poly(ethylene glycol) (PEG‐Biotin) and streptavidin‐functionalized hyaluronic acid (HA‐Streptavidin). The polysaccharide nanoparticles were noncovalently assembled via electrostatic interactions between low‐molecular‐weight heparin (LMWH) and N,N,N‐trimethylchitosan chloride (TMC). Vascular endothelial growth factor (VEGF) was entrapped in the LMWH/TMC nanoparticles by affinity interactions with LMWH.     

Nanotemplate Engineering of Cell Specific Nanoparticles

Abstract

Through nanotechnology, it is now possible to cost‐effectively and reproducibly create and develop useful small particles for applications in the pharmaceutical, medical, chemical, and engineering fields. In the pharmaceutical field, cost‐effective, reproducible, and scalable processes to engineer cell‐ or tissue‐targeted nanoparticles are sought to deliver potent drugs as new therapies. A natural and spontaneous method to engineer nanoparticles has been developed through the use of microemulsions whereby the dispersed phase droplets serve as “nanotemplates” to directly form stable nanoparticles. The present review will serve to provide an overview of the challenges and opportunities in developing ideal nanoparticulate carrier systems and the use of microemulsion precursors to engineer nanoparticles. An overview will be presented on our work in targeting surface‐modified nanoparticles to (1) dendritic cells for potential new types of genetic and subunit protein vaccines, and (2) solid tumors for potential neutron capture therapy (NCT) using gadolinium.     

Construction of Deoxyribonucleic Acid Decorated Gold Nanostructures as Nanomedical Agents

Gold nanoparticles provide promising applications based on their versatile properties of electromagnetic scattering and absorption and the capability of photothermal transduction relying on their size and shape. Because of their high tolerance to the environment and their excellent biocompatibility, gold nanoparticles are the most recognized nanomaterial applied in biomedicine. Deoxyribonucleic acid (DNA) is a native biomaterial that stores genetic information in living organisms. Naturally, DNA can be combined with gold nanoparticles for a variety of biomedical purposes. For example, the reversible hydrogen bonding of the complementary double‐stranded structures has been employed to serve as a gate keeper for the control of drug release on demand. Besides, the complementary hybridization behavior has given the specific recognition in nucleic acid for sensing feature. Accordingly, this mini‐review describes how DNA–gold nanoconjugates have been formulated and aimed for drug release and sensing analysis as well as the hybrids of aptamer–gold analogy for biomedical studies. These nanoconjugates show the potential for preclinical and clinical treatments.     

Organic carbonates as stabilizing solvents for transition-metal nanoparticles

Biodegradable, non-toxic, "green" and inexpensive propylene carbonate (PC) solvent is shown to function as a stabilizing medium for the synthesis of weakly-coordinated transition-metal nanoparticles. Kinetically stable nanoparticles (M-NPs) with a small and uniform particle size (typically <5 ± 1 nm) have been reproducibly obtained by easy, rapid (3 min) and energy-saving 50 W microwave irradiation under an argon atmosphere from their metal-carbonyl precursors in PC. The M-NP/PC dispersions are stable for up to three weeks according to repeated TEM studies over this time period. The rhodium nanoparticle/PC dispersion is a highly active catalyst for the biphasic liquid-liquid hydrogenation of cyclohexene to cyclohexane with activities of up to and 1875 (mol product) (mol Rh)(-1) h(-1) and near quantitative conversion at 4 to 10 bar H(2) and 90 °C. From the PC dispersion the M-NPs can be coated with organic capping ligands such as 3-mercaptopropionic acid or trioctylphosphine oxide for further stabilization.     

Polymeric Nanoparticles Induce NLRP3 Inflammasome Activation and Promote Breast Cancer Metastasis

Polymeric nanoparticles gain enormous interests in cancer therapy. Polyethylenimine (PEI) 25 kD is well known for its high transfection efficiency and cytotoxicity. PEI‐CyD (PC) was previously synthesized by conjugating low molecular PEI (M _w 600) with β‐cyclodextrin (β‐CyD), which is shown to induce lower cytotoxicity than PEI 25 kD. In the current study, the in vivo immune response of branched PEI 25 kD and PC is investigated. Compared to PC/pDNA, exposure of PEI 25kD/pDNA induces higher level of immune‐stimulation evidenced by the increased spleen weight, phagocytic capacity of peritoneal macrophage, and proinflammatory cytokines in serum and liver. Importantly, administration of PEI 25 kD can greatly promote breast cancer metastasis in liver and lung tissues, which correlates with its ability to induce high oxidative stress and NLRP3‐inflammasome activation. These results suggest that polymeric nanocarriers have the potential to induce immune‐stimulation and cancer metastasis, which may affect their efficiency for cancer therapy.     

A Universal Approach for the Reversible Phase Transfer of Hydrophilic Nanoparticles

The ability to engineer the surface properties of magnetic nanoparticles is important for their various applications, as numerous physical and chemical properties of nanoscale materials are seriously affected by the chemical constitution of their surfaces. For some specific applications, nanoparticles need to be transferred from a polar to a nonpolar environment (or vice versa) after synthesis. In this work we have developed a universal method for the phase transfer of magnetic nanoparticles that preserves their shape and size. Octadecyltrimethoxysilane was used to cap the surfaces of the aqueous magnetic nanoparticles, thereby allowing their transfer into nonpolar solution. The resulting hydrophobic magnetic nanoparticles were transferred back into aqueous solution by subsequently covering them with an egg‐PC lipid monolayer. The superparamagnetic properties of the particles were retained after the phase transfer. The maximum transfer yields are dependent on their particle size with a maximum value of 93.16±4.75 % for magnetic nanoparticles with a diameter of 100 nm. The lipid‐modified magnetic particles were stable over 1 week, and thus they have potential applications in the field of biomedicine. This work also provides a facile strategy for the controllable engineering of the surface properties of nanoparticles.     

Modern Inorganic Aerogels

Essentially, the term aerogel describes a special geometric structure of matter. It is neither limited to any material nor to any synthesis procedure. Hence, the possible variety of materials and therefore the multitude of their applications are almost unbounded. In fact, the same applies for nanoparticles. These are also just defined by their geometrical properties. In the past few decades nano‐sized materials have been intensively studied and possible applications appeared in nearly all areas of natural sciences. To date a large variety of metal, semiconductor, oxide, and other nanoparticles are available from colloidal synthesis. However, for many applications of these materials an assembly into macroscopic structures is needed. Here we present a comprehensive picture of the developments that enabled the fusion of the colloidal nanoparticle and the aerogel world. This became possible by the controlled destabilization of pre‐formed nanoparticles, which leads to their assembly into three‐dimensional macroscopic networks. This revolutionary approach makes it possible to use precisely controlled nanoparticles as building blocks for macroscopic porous structures with programmable properties.