Small Hydrodynamic Diameter Research Articles

Self-aggregation effect of the ternary system “Alga EPS-DOM-HMs” and the characterization of the self-adaptation metabolic response of microalgae

Heavy metals (HMs) present in the natural aquatic environment can form a ternary aggregate of “EPS-DOM-HMs” with the prevalent microalgae extracellular polymers substances (EPS) and macromolecular dissolved organic matters (DOMs), which show special molecular structure and biological interaction. This study reveals the formation of “EPS-TA-HMs” and the mechanism of their physiological and metabolic effects on Raphidocelis subcapitata. Results indicate that TA-Cr(III) can bind to EPS to form ternary aggregates with substances coexisting large and small hydrodynamic diameters and that the interactions are dominated by hydrophobic interactions of the protein binding to the pyrrole ring of the polyphenol and hydrogen bonding interactions formed by OC–(N R O). The protein structure of EPS has the largest proportion of proline, glycine, aspartic acid, and tryptophan. These interactions promoted the secretion of EPS components and reduced the growth inhibition of Raphidocelis subcapitata by 45.9 % compared with Cr(III) exposure. TEM analysis combined with EDS analysis indicated that Cr(III) was taken intracellularly and TA-Cr(III) was not. In addition, metabolomics analyses revealed that microalgae initiate adaptive mechanisms via the activation of a two-component system (i.e., maintenance of high metabolic activity). This study underscored the morphology of HMs in real aquatic environments and the mechanisms of metabolic effects on aquatic organisms.

Chiral‐induced highly efficient NIR–photothermal conversion of perylene diimide@silica nanocapsules for photothermal therapy

AbstractPhotothermal agents (PTAs) with ultra‐high photothermal conversion efficiency (PCE) activated upon near‐infrared (NIR) laser irradiation can heat up and destroy tumor cells under low‐intensity laser excitation to allow safe and efficient tumor therapy. Herein, an organic PTA with an outstanding PCE of 89.6% is developed from rationally designed perylene diimide (PDI) with electron‐donating cyclohexylamine moiety at the bay‐positions of its skeleton and chiral phenethylamine (PEA) moiety at its N terminals, termed here PEAPDI. The strong intermolecular interaction between the PDI skeletons induced by PEA together with the intramolecular charge transfer from cyclohexylamine to PDI skeleton severely quenches the fluorescence emission from PEAPDI and significantly enhances its NIR absorption, resulting in super NIR–photothermal conversion. PEAPDI molecules are subsequently encapsulated within silica nanocapsules (SNCs), creating PEAPDI@SNC. Characterized by its small hydrodynamic diameter, monodispersity, high PDI encapsulation efficiency, colloidal stability, and biocompatibility, PEAPDI@SNC exhibits prolonged blood circulation and enhanced permeability and retention effect, enabling targeted accumulation at the tumor site. An in vivo study using a 4T1 tumor–bearing mice model illustrates the agent's potent tumor ablation capability without side effects at low dosage under NIR laser irradiation (808 nm). The findings demonstrate PEAPDI@SNC's significant potential as a PTA for tumor treatment.

Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J-Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging.

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.

Insight into the effect of synthesis parameters on the properties of graphene quantum dots for theranostic application

Ultra-small size and tunable optical properties of graphene quantum dots (GQDs) make them potentially suitable for theranostic applications. This investigation focuses on the effect of process parameters for the synthesis of GQDs of desirable optical properties for biomedical applications. The effect of the raw materials (graphene oxide sheets, glucose, and starch), reaction temperature (170 to 200 °C), and reaction time (3 to 6 h) was investigated on GQDs prepared through hydrothermal treatment. The dispersion of GQDs was characterized using dynamic light scattering (DLS), UV–visible, fluorescence, Raman, and X-ray photon spectroscopic techniques. The effect of the solution temperature and pH on the fluorescence properties of GQDs was also studied. The small hydrodynamic diameter (8.57 ± 1.47 nm) was observed with GQDs prepared from glucose using hydrothermal treatment time of 4 h at 190 °C (GQDs-D). The GQDs-D showed blue fluorescence (λem= 460 nm) with a quantum yield (QY) 67.09 ± 1.25%. The fluorescence characteristic of the GQDs was unchanged up to 6 months during storage at room temperature. GQDs-D revealed their antioxidant nature with a DPPH scavenging activity of 15.08 ± 2.07%. Despite having relatively low DPPH scavenging activity, excellent hemocompatibility (0.23 ± 0.04%) and colloidal stability against bovine serum albumin (BSA) showed GQDs-D as a safe nanocarrier for theranostic application. This was further substantiated with circular dichroism (CD) spectroscopy, which exhibited a preserved α-helical structure of BSA by GQDs-D. High-resolution transmission electron microscopic image of GQDs-D showed an average particle size of 5.70 nm and homogeneous particle distribution between 2–8 nm. Conclusively, all the results revealed the potential of GQDs-D for theranostic application.

Nanogels with covalently bound and releasable trehalose for autophagy stimulation in atherosclerosis

Atherosclerosis, cholesterol-driven plaque formation in arteries, is a complex multicellular disease which is a leading cause of vascular diseases. During the progression of atherosclerosis, the autophagic function is impaired, resulting in lipid accumulation-mediated foam cell formation. The stimulation of autophagy is crucial for the recovery of cellular recycling process. One of the potential autophagy inducers is trehalose, a naturally occurring non-reducing disaccharide. However, trehalose has poor bioavailability due to its hydrophilic nature which results in poor penetration through cell membranes. To enhance its bioavailability, we developed trehalose-releasing nanogels (TNG) for the treatment of atherosclerosis. The nanogels were fabricated through copolymerization of 6-O-acryloyl-trehalose with the selected acrylamide-type monomers affording a high trehalose conjugation (~ 58%, w/w). TNG showed a relatively small hydrodynamic diameter (dH, 67 nm) and a uniform spherical shape and were characterized by negative ζ potential (-18 mV). Thanks to the trehalose-rich content, TNG demonstrated excellent colloidal stability in biological media containing serum and were non-hemolytic to red blood cells. In vitro study confirmed that TNG could stimulate autophagy in foam cells and enhance lipid efflux and in vivo study in ApoE−/− mice indicated a significant reduction in atherosclerotic plaques, while increasing autophagic markers. In conclusion, TNG hold great promise as a trehalose delivery system to restore impaired autophagy-mediated lipid efflux in atherosclerosis and subsequently reduce atherosclerotic plaques.Graphical abstract

Food Additive Solvents Increase the Dispersion, Solubility, and Cytotoxicity of ZnO Nanoparticles.

Zinc oxide (ZnO) nanoparticles (NPs) are utilized as a zinc (Zn) fortifier in processed foods where diverse food additives can be present. Among them, additive solvents may strongly interact with ZnO NPs by changing the dispersion stability in food matrices, which may affect physico-chemical and dissolution properties as well as the cytotoxicity of ZnO NPs. In this study, ZnO NP interactions with representative additive solvents (methanol, glycerin, and propylene glycol) were investigated by measuring the hydrodynamic diameters, solubility, and crystallinity of ZnO NPs. The effects of these interactions on cytotoxicity, cellular uptake, and intestinal transport were also evaluated in human intestinal cells and using in vitro human intestinal transport models. The results revealed that the hydrodynamic diameters of ZnO NPs in glycerin or propylene glycol, but not in methanol, were significantly reduced, which is probably related to their high dispersion and increased solubility under these conditions. These interactions also caused high cell proliferation inhibition, membrane damage, reactive oxygen (ROS) generation, cellular uptake, and intestinal transport. However, the crystal structure of ZnO NPs was not affected by the presence of additive solvents. These findings suggest that the interactions between ZnO NPs and additive solvents could increase the dispersion and solubility of ZnO NPs, consequently leading to small hydrodynamic diameters and different biological responses.

Preparation and optimization of hyaluronic acid decorated irinotecan-loaded poly(lactic-co-glycolic acid) nanoparticles by microfluidics for cancer therapy applications

Polymer-based nanoparticles have been largely investigated in the cancer therapy field for their features to generate colloidal delivery systems of hydrophobic drugs to improve drug stability, specific delivery and reduce toxicity. In particular, nanoparticles surface functionalized with hyaluronic acid have been widely employed for their active tumor-targeting efficiency. Furthermore, the control of the physicochemical properties as well as high drug encapsulation efficiency, yield and batch-to-batch reproducibility of nanoparticles obtained by means of microfluidics, pave the way to overcome the drawbacks related to the fabrication of NPs obtained via traditional bulk methods and consequently increase cancer cell killing effect. For these reasons, we here investigated the effects of process parameters on the preparation and optimization of poly(lactic-co-glycolic acid)-poloxamers nanoparticle formulations (PLGA/PF68+PF127 NPs) decorated with HA (HA-based NPs) by using microfluidics for intravenous delivery of a model chemotherapeutic agent, irinotecan (IRIN). The study on the aggregation behavior and morphology of NPs were investigated by Dynamic Light Scattering (DLS), Electrophoretic Light Scattering (ELS), Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC). Our results revealed that by increasing the polymer weight fractions of organic and water phases the size, the NP yield, and the drug encapsulation efficiency of NPs are increased. Furthermore, by increasing the flow rate ratios from 0.05 to 0.3, a raise of dH from ∼85.6 to ∼176.4, for PLGA/PP NPs, and from ∼101.6 to ∼283.3 for HA/PLGA/PP is detected. The optimized HA-based NP formulation showed a spherical morphology, with a core-shell structure, small hydrodynamic diameter (dH∼120 nm), uniform size distribution (PDI<0.06) and high: i) drug loading (DL∼22.7%), ii) drug encapsulation efficiency (DEE∼87.8%) and iii) yield (92.4%). Moreover, the in vitro IRIN kinetic release and stability of IRIN-loaded HA-based NPs were evaluated showing the complete release in 15 days. Thus, this study highlighted a microfluidic method to fabricate IRIN-loaded HA-based NPs without any chemical modifications to provide novel understanding of the effect of process parameters, by varying the polymer weight fractions of both organic and water phases and flow rate ratio, on the physicochemical properties and consequently on nanoparticle formulation qualities for cancer therapy applications.

Sargassum horneri extracts loaded nanostructured lipid carriers: Preparation, physicochemical properties, and in vitro antioxidant activity studies

This study tried to establish optimal conditions for Sargassum horneri extracts loaded nanostructured lipid carriers (SHE-NLCs). Therefore, we observed various physicochemical analyzes, sugar and phenolic contents, and antioxidants while storing the SHE-NLCs for 28 days at different SHE addition amounts (0%–0.5%) and storage temperatures (25 and 65 °C). All SHE-NLCs stored at 25 °C showed a small hydrodynamic diameter (20.1–25.4 nm) and high encapsulation efficiency (64.1%–89.3%) for 28 days. As the amount of SHE increased, the pH and electrical conductivity of SHE-NLCs significantly decreased and increased, respectively (p < 0.05). Also, at 25 °C, prevented a sharp decrease in the total phenolic content and antioxidant activity of SHE-NLCs as the storage period increased compared to 65 °C. SHE 0.25% loaded NLCs can stably maintain the formulation structure for 28 days at room temperature while being an amount sufficiently containing the functionality of SHE.

Development of Polyurethane/Peptide-Based Carriers with Self-Healing Properties.

In situ-forming gels with self-assembling and self-healing properties are materials of high interest for various biomedical applications, especially for drug delivery systems and tissue regeneration. The main goal of this research was the development of an innovative gel carrier based on dynamic inter- and intramolecular interactions between amphiphilic polyurethane and peptide structures. The polyurethane architecture was adapted to achieve the desired amphiphilicity for self-assembly into an aqueous solution and to facilitate an array of connections with peptides through physical interactions, such as hydrophobic interactions, dipole-dipole, electrostatic, π-π stacking, or hydrogen bonds. The mechanism of the gelation process and the macromolecular conformation in water were evaluated with DLS, ATR-FTIR, and rheological measurements at room and body temperatures. The DLS measurements revealed a bimodal distribution of small (~30-40 nm) and large (~300-400 nm) hydrodynamic diameters of micelles/aggregates at 25 °C for all samples. The increase in the peptide content led to a monomodal distribution of the peaks at 37 °C (~25 nm for the sample with the highest content of peptide). The sol-gel transition occurs very quickly for all samples (within 20-30 s), but the equilibrium state of the gel structure is reached after 1 h in absence of peptide and required more time as the content of peptide increases. Moreover, this system presented self-healing properties, as was revealed by rheological measurements. In the presence of peptide, the structure recovery after each cycle of deformation is a time-dependent process, the recovery is complete after about 300 s. Thus, the addition of the peptide enhanced the polymer chain entanglement through intermolecular interactions, leading to the preparation of a well-defined gel carrier. Undoubtedly, this type of polyurethane/peptide-based carrier, displaying a sol-gel transition at a biologically relevant temperature and enhanced viscoelastic properties, is of great interest in the development of medical devices for minimally invasive procedures or precision medicine.

Novel amphiphilic hydroxyethyl starch-based nanoparticles loading camptothecin exhibit high anticancer activity in HepG2 cells and zebrafish

Camptothecin is a naturally occurred anticancer drug but exhibits limitations including poor aqueous solubility, low bioavailability, and high level of adverse drug reactions on normal organs. To overcome these problems, this paper developed a novel amphiphilic Lau-Leu-HES carrier using hydroxyethyl starch, lauric acid, and L-leucine as starting materials. The carrier was successfully applied to prepare Lau-Leu-HES nanoparticles loading camptothecin. The drug loading efficiency and encapsulation efficiency of the nanoparticles were calculated to be 29.04% and 81.85%, respectively. The nanoparticles exhibited high zeta potential (–15.51 mV) and small hydrodynamic diameter (105.4 nm). Camptothecin in nanoparticles could be rapidly released under acidic condition (pH = 4.5), thereby indicating the high sensitivity under cancer microenvironments. Anticancer investigation revealed that the nanoparticles could inhibit the proliferation of HepG2 cells in vitro. Compared with commercial available drug doxorubicin, the nanoparticles could significantly inhibit the expression of krasv12 oncogene in transgenic Tg (EGFP-krasV12) zebrafish. These results indicate that the camptothecin-loaded Lau-Leu-HES nanoparticles are expected to be a potential candidate for cancer therapy.

Effects of Chitosan Molecular Weight and Degree of Deacetylation on Chitosan-Cellulose Nanocrystal Complexes and Their Formation.

This study was conducted to determine the effects of chitosan molecular weight and degree of deacetylation (DD) on chitosan-cellulose nanocrystal (CNC) polyelectrolyte-macroion complexes (PMCs) and their formation. Chitosan samples with three different molecular weights (81, 3 · 103, 6 · 103 kDa) and four different DDs (77, 80, 85, 89%) were used. The effects on PMC formation were determined by turbidimetric titration. An effect of the molecular weight of chitosan was not observed in turbidimetric titrations. Turbidity levels were higher for CNCs with lower sulfate group density and larger hydrodynamic diameter than for CNCs with higher sulfate group density and smaller hydrodynamic diameter. Conversely, turbidity levels were higher for chitosans with higher DD (higher charge density) than for chitosans with lower DD (lower charge density). PMC particles from chitosans with different molecular weights were characterized by scanning electron microscopy, laser Doppler electrophoresis, and dynamic light scattering. PMCs from high-molecular-weight chitosan were more spherical and those from medium-molecular-weight chitosan had a slightly larger hydrodynamic diameter than PMCs from the respective other two chitosans. The molecular weight of the chitosan was concluded to have no effect on the formation of chitosan-CNC PMC particles and only a minor effect on the shape and size of the particles. The higher turbidity levels for CNCs with lower sulfate group density and larger hydrodynamic diameter and for chitosans with higher DD were attributed to a larger number of CNCs being required for charge compensation.

Glycerol-compressed self-assembly nanogel based on ovomucin and chito-oligosaccharide: A novel green strategy for curcumin delivery

Nano-gel technology has been one of the popular methods to solve the low bioavailability of hydrophobic active substances. In this work, Ovomucin (OVM) was combined with chito-oligosaccharide (COS) by self-assembly, followed by condensation of complexes initiated via glycerol solution to produce green nanogel delivering curcumin. The successful encapsulation of curcumin was confirmed by UV–Vis spectrum and fluorescence microscopy. In addition, the morphology of the nanogel was nearly spherical with a small average hydrodynamic diameter (115.43nm), uniform particle size distribution (PDI = 0.266), and intense surface negative charge (−23.56mV). The vitro-release simulation assay showed that the nano-gels have good sustained release ability. The antioxidant activities of free curcumin and curcumin-loaded nano-gels were investigated by ABTS, DPPH, and H 2 O 2. The results of FTIR and XRD confirmed that curcumin disperses uniformly in the whole system through hydrogen bond and hydrophobic interaction between the nanogel. Curcumin in nanogel enabled easier access to free radicals in water phase, thereby possessing stronger antioxidant activity than free curcumin. Furthermore, cytotoxicity test results showed that nanogel has no obvious toxicity signs on cell viability. Hence, this work holds a grand promise for safe and efficient oral curcumin delivery while possessing universal significance for the extension of using OVM as an efficient and functional encapsulating agent to broad applications in food and health industries. OVM was mixed with curcumin and bound to each other by hydrophobic interaction and hydrogen bond. COS induced the formation of early nanogel by electrostatic action. Glycerol compressed the gel to produce the final nanogel. • The nanogel was synthesized in a green way by glycerol compression and self-assembly. • The average hydrodynamic diameter of curcumin-loaded OVM nanogel was only 115.43 ± 1.60 nm and size distribution was narrow. • The fluorescence quenching of the nanogel confirmed the encapsulation of curcumin. • The Cur-OVM-COS nanogel showed a better sustained-release effect during simulated gastrointestinal digestion than the free curcumin. • The antioxidant activity of encapsulated curcumin was improved.

Thermoresponsive Reversible Unimer Micelles of Amphiphilic Fluorinated Copolymers

AbstractAmphiphilic fluorinated copolymers PEGMAx‐co‐FAy and TEGMAx‐co‐FAy are prepared by activators regenerated by electron transfer atom transfer radical polymerization (ARGET‐ATRP). All polymers present a reversible thermoresponsive lower critical solution temperature‐type behavior, and a cloud point temperature (Tc) in the range of 30–60 °C strictly dependent on the length of the oxyethylene side chain, the content of the hydrophobic counits, and the concentration of the solution. Combined small angle X‐ray scattering (SAXS) and dynamic light scattering measurements are used to study the self‐assembly behavior in water, organic solvents (tetrahydrofuran [THF] and dimethylformamide [DMF]), and a fluorinated solvent (hexafluorobenzene [HFB]). SAXS confirms the formation of compact‐globular single‐chain self‐folded unimer micelles in water below Tc, which generally presents small hydrodynamic diameters (Dh ≤ 8 nm) as a result of the folding of the hydrophobic perfluorohexylethyl acrylate counits. The copolymers are also able to form reverse unimer micelle in HFB. The copolymers are not able to self‐assemble in unimer micelles in THF or DMF solutions, in which they adopt conventional random coil conformations.

Phenethyl Isothiocyanate-Conjugated Chitosan Oligosaccharide Nanophotosensitizers for Photodynamic Treatment of Human Cancer Cells.

The aim of this study is to synthesize phenethyl-conjugated chitosan oligosaccharide (COS) (abbreviated as ChitoPEITC) conjugates and then fabricate chlorin E6 (Ce6)-incorporated nanophotosensitizers for photodynamic therapy (PDT) of HCT-116 colon carcinoma cells. PEITC was conjugated with the amine group of COS. Ce6-incorporated nanophotosensitizers using ChitoPEITC (ChitoPEITC nanophotosensitizers) were fabricated by dialysis method. 1H nuclear magnetic resonance (NMR) spectra showed that specific peaks of COS and PEITC were observed at ChitoPEITC conjugates. Transmission electron microscope (TEM) confirmed that ChitoPEITC nanophotosensitizers have spherical shapes with small hydrodynamic diameters less than 200 nm. The higher PEITC contents in the ChitoPEITC copolymer resulted in a slower release rate of Ce6 from nanophotosensitizers. Furthermore, the higher Ce6 contents resulted in a slower release rate of Ce6. In cell culture study, ChitoPEITC nanophotosensitizers showed low toxicity against normal CCD986Sk human skin fibroblast cells and HCT-116 human colon carcinoma cells in the absence of light irradiation. ChitoPEITC nanophotosensitizers showed a significantly higher Ce6 uptake ratio than that of free Ce6. Under light irradiation, cellular reactive oxygen species (ROS) production of nanophotosensitizers was significantly higher than that of free Ce6. Especially, PEITC and/or ChitoPEITC themselves contributed to the production of cellular ROS regardless of light irradiation. ChitoPEITC nanophotosensitizers showed significantly higher PDT efficacy against HCT-116 cells than that of free Ce6. These results indicate that ChitoPEITC nanophotosensitizers have superior potential in Ce6 uptake, ROS production and PDT efficacy. In the HCT-116 cell-bearing mice tumor-xenograft model, ChitoPEITC nanophotosensitizers efficiently inhibited growth of tumor volume rather than free Ce6. In the animal imaging study, ChitoPEITC nanophotosensitizers were concentrated in the tumor tissue, i.e., fluorescence intensity in the tumor tissue was stronger than that of other tissues. We suggest that ChitoPEITC nanophotosensitizers are a promising candidate for the treatment of human colon cancer cells.

(Keynote) Quantum Dot Coatings for Aqueous Stabilization and Applications in Biomolecular Analysis

Semiconductor quantum dots have been commercially available as molecular probes for applications in the life sciences and clinical diagnostics for two decades, however they have only been adopted in niche applications. Part of the reason for limited adoption is attributable to challenges in colloidal stabilization, as these solid nanocrystals tend to aggregate and nonspecifically adsorb to surfaces and cellular structures. This can largely be alleviated by use of nanocrystal coatings that resist nonspecific binding and promote aqueous dispersion, however the vast majority of such coatings are based on neutral and zwitterionic polymers that add considerable hydrodynamic size to the product. This size increase is due to the bulk of the coating itself as well as adsorption of water molecules and ions in solution. The size increase causes steric hindrance and inaccurate molecular labeling when these probes are used to analyze targets that have considerable size or ones that are located in crowded regions of cells or tissues. Furthermore, the bioaffinity label that attaches the quantum dot to its intended molecular target often contributes substantially to the final size and stability of the probe. This is especially challenging for protein labeling using antibodies, which themselves are fairly large proteins that attach heterogeneously to quantum dots, typically yielding large, polydisperse products. This talk will focus on developments in quantum dot engineering, monolayer polymeric coatings, and bioconjugation strategies to optimize offsetting characteristics of size, homogeneity, bioaffinity, and specificity. In particular, multidentate polymer coatings in recent years have enabled the production of quantum dots with long-term shelf life, small hydrodynamic diameters, and efficient click chemistry conjugations. By tuning the conjugation methods to antibody fragments and single-stranded DNA, we can now prepare bioaffinity labels for proteins and nucleic acids in the ~10 nm range, with further size reductions possible through nanocrystal heterostructure engineering. This talk will also cover how in situ protein and nucleic acid labeling applications can benefit from these advances in addition to current challenges in processing, scale-up, and user adoption.

Ultrasmall Superparamagnetic Iron Oxide Nanoparticles as Nanocarriers for Magnetic Resonance Imaging: Development and In Vivo Characterization.

Ultrasmall superparamagnetic iron oxide nanoparticles (uSPIOs) are attractive platforms for the development of smart contrast agents for magnetic resonance imaging (MRI). Oleic acid-capped uSPIOs are commercially available yet hydrophobic, hindering in vivo applications. A hydrophilic ligand with high affinity toward uSPIO surfaces can render uSPIOs water-soluble, biocompatible, and highly stable under physiological conditions. A small overall hydrodynamic diameter ensures optimal pharmacokinetics, tumor delivery profiles, and, of particular interest, enhanced T 1 MR contrasts. In this study, for the first time, we synthesized a ligand that not only fulfills the as-proposed properties but also provides multiple reactive groups for further modifications. The synthesis delivers a facile approach using commercially available reactants, with resultant uSPIO-ligand constructs assembled through a single-step ligand exchange process. Structural and molecular size analyses confirmed size uniformity and small hydrodynamic diameter of the constructs. On average, 43 reactive amine groups were present per uSPIO nanoparticle. Its r 1 relaxivity has been tested on a 7 Tesla MR instrument and is comparable to that of the clinically available T 1 gadolinium-based contrast agent GBCA (1 vs 3 mM-1 s-1, respectively). A significant decrease in tumor T1 (15%) within 1 h of injection and complete signal recovery after 2 h were detected with a dose of 7 μg Fe/g mouse. The agent also has high r 2 relaxivity and can be used for T 2 contrast-enhanced MRI. Taken together, good relaxation and delivery properties and the presence of multiple surface reactive groups can facilitate its application as a universal MRI-compatible nanocarrier platform.

Antimicrobial activity of lactoferrin-chitosan-gellan nanoparticles and their influence on strawberry preservation

Lactoferrin (L), chitosan (C) and gellan (G) nanoparticles were produced by electrostatic complexation, aiming to enhance the antimicrobial characteristics of these compounds. Binary complexes (lactoferrin-gellan and chitosan-gellan) and ternary complexes (lactoferrin-chitosan-gellan) were studied in eight different proportions of biopolymers. The antimicrobial activity of nanoparticles against S. aureus was compared with that of pure biopolymers and related to nanoparticle size, charge density and morphology. Those with a 4.5L:4.5C:1G ratio presented the highest positive charge density (+57.90 ± 1.50) mV and smaller hydrodynamic diameter (53.53 ± 2.06) nm, which resulted in the highest antimicrobial action (minimum inhibitory concentration of 0.0117 mg/ml). When applied to a coating of fresh strawberries, the nanoparticles were effective in preserving their physicochemical properties, especially in the presence of carboxymethylcellulose that enhanced the adhesion of particles to the fruits. In this study, the antimicrobial action of nanoparticles was better than that of lactoferrin and pure chitosan alone, proving that the antimicrobial properties of such biopolymers were enhanced due to aggregation at the nanoscale. The nanoparticles produced have outstanding application potential as natural food preservers.

Physical Characterization and Cellular Toxicity Studies of Commercial NiO Nanoparticles.

Nickel oxide (NiO) nanoparticles from several manufacturers with different reported sizes and surface coatings were characterized prior to assessing their cellular toxicity. The physical characterization of these particles revealed that sizes often varied from those reported by the supplier, and that particles were heavily agglomerated when dispersed in water, resulting in a smaller surface area and larger hydrodynamic diameter upon dispersion. Cytotoxicity testing of these materials showed differences between samples; however, correlation of these differences with the physical properties of the materials was not conclusive. Generally, particles with higher surface area and smaller hydrodynamic diameter were more cytotoxic. While all samples produced an increase in reactive oxygen species (ROS), there was no correlation between the magnitude of the increase in ROS and the difference in cytotoxicity between different materials.

Impact of alginate block type on the structure and physicochemical properties of curcumin-loaded complex biopolymer nanoparticles

In this study, core-shell complex biopolymer nanoparticles loaded with curcumin were fabricated using a simple pH-driven method. An aqueous solution containing curcumin, zein, sodium caseinate, and sodium alginate was prepared under a strongly alkaline condition (pH 12) and then acidified (pH 4). This led to the formation of curcumin-loaded complex biopolymer nanoparticles with a hydrophobic core (zein) surrounded by a hydrophilic shell (caseinate-alginate). The nanoparticles formed from β-d-mannuronic acid residues blocks (MM-blocks) had the smallest hydrodynamic diameter (202 nm), highest encapsulation efficiency (98 g/100 g), and best water-dispersibility. Transmission electron microscopy showed that the complex biopolymer nanoparticles had a core-shell structure. Fluorescence and FTIR spectroscopy were used to provide insights into the nature of the molecular hydrogen bonding and electrostatic interactions within the complex biopolymer nanoparticles. Overall, the curcumin-loaded complex biopolymer nanoparticles fabricated from MM-blocks had the best long-term storage and salt stability. These results may be useful for creating colloidal delivery systems that enhance the dispersibility, stability, and bioactivity of hydrophobic nutraceuticals.

Amine as a bottom-line functionality on DDS surface for efficient endosomal escape and further subcellular targets

Subcellular targeting of drug delivery system (DDS) and hence delivery of drugs to individual organelles enhance efficacy, efficiency and effectiveness of drug treatment, and subsequently trim adverse cytotoxic effects. But efficient subcellular targeting is often limited due to their endosomal trapping and lysosomal degradation. Here we report a pilot study using quantum dot (QD) based smart nanoparticle as model DDS of small hydrodynamic diameter that can escape endosome efficiently due to surface amine functionalities having weak basic properties on its surface and target to the cell nucleus. We have synthesized high quality QD using colloidal synthesis technique and introduced optimum ratio of primary, secondary and tertiary amines on their surface using surface decoration strategies, having high cellular uptake and efficient endosomal escape property and trafficked to cell nucleus after functionalization with TAT peptide. Our developed polymeric coating chemistry has been exploited for the extensive variation and finer adjustment of different amine functionalities on the DDS surface. Developed amine functionalization method is simple, versatile, adjustable for further functional variations and extendable to different DDS.