Nanoparticles: Synthesis, Surface Modification and Functionalization for Biological and Environmental Applications

In addition to the type or nature of the nanoparticles (NPs) core, the surface of the obtained nanoparticles plays a crucial role and has great impact on the physicochemical properties of the nanoparticles which reflect in turn on the nanomaterials interactions (with the surrounding medium, biological systems and environment), functionalities and their possible applications. The general focus of this doctoral dissertation has been paid to the synthesis, controlled surface modification, functionalization, purification and characterization of different types of (plasmonic, semiconductor and magnetic) nanoparticles providing water soluble and highly colloidally stable nanoparticles proper for environmental and biological applications. Most of the as synthesized nanoparticles are inorganic particles (e.g. 5 nm Au NPs, 12 nm magnetic iron oxide NPs, 3 nm iron platinum NPs, 8 nm cobalt platinum NPs, CdSe/ZnS core/shell QDs of different sizes from 3-5 nm to 7 nm ZnO QDs) stabilized by hydrophobic organic molecules known as the surfactant or ligand which play an important role to control the shape and growth of the during the nanoparticles synthesis in addition to its role as stabilizing agents preventing the nanoparticles to be agglomerated. In case of water insoluble (hydrophobically capped) nanoparticles (not suitable for the biological applications), they were transformed from organic phase to aqueous environment using a very general protocol known as amphiphilic polymer coating which is based on the hydrophobic interaction between the hydrophobic ligands on the surface of the nanoparticles and the hydrophobic side chains of the used polymer. The polymer coating of originally organic-solvent soluble nanoparticles converts them to water soluble ones (thanks to the free carboxylate groups on surface) which have the ability to be further functionalized with extra functional and/or biologically active molecules of interest. The obtained polymer coated nanoparticles were purified and characterized using different techniques, such as agarose gel electrophoresis, size exclusion chromatography, UV-Vis spectroscopy, fluorescence spectroscopy (in case of fluorescent materials), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Monodisperse different types of polymer coated nanoparticles were obtained with a high quality and colloidal stability as inferred from their physicochemical properties such as narrow hydrodynamic diameter distribution and the negative surface charges expressed as zeta potential. Furthermore, the surface of some water soluble polymer coated nanoparticles was modified with different functionalities such as some fluorophores (e.g. Dy-495, DY-647 and rhodamine), polyethylene glycol, folic acid and methotrexate to obtain multifunctional nanoparticles that could be useful for a wide range of biological applications such as tracking, labeling and multimodal imaging and targeting drug delivery

Rapid Green Synthesis of Metal Nanoparticles using Pomegranate Polyphenols

Plant extract could be an alternative to traditional chemical methods for the production of metallic nanomaterials in a clean, nontoxic and ecologically sound manner. In the present study, we aimed to develop a rapid ecofriendly method for the synthesis of both silver and gold nanoparticles using pomegranate peel extract (PPE). The bioactive constitutes and the potential antioxidant capacity of pomegranate (Punica granatum L.) extract seems to play a role in the production of metal nanoparticles. Biosynthesis of metal nanoparticles using PPE gives high yield of nanoparticles. The resulted nanoparticles provided high monodisperse character with an average particle size 50 nm for gold nanoparticles and 20 nm for silver nanoparticles

Versatile Route for Multifunctional Aerogels Including Flaxseed Mucilage and Nanocrystals

Preparation of low density monolithic and free-standing organic-inorganic hybrid aerogels of various properties is demonstrated using green chemistry from a biosafe natural source (flaxseed mucilage) and freeze-casting and subsequent freeze drying. Bio-aerogels, luminescent aerogels, and magneto-responsive aerogels are obtained by combination of the flaxseed mucilage with different types of nanoparticles. Moreover, the aerogels are investigated as possible drug release systems using curcumin as a model. Various characterization techniques like thermogravimetric analysis, nitrogen physisorption, electron microscopy, UV/Vis absorption, and emission spectroscopy, bulk density, and mechanical measurements, as well as in vitro release profile measurements, are employed to investigate the obtained materials. The flaxseed-inspired organic-inorganic hybrid aerogels exhibit ultra-low densities as low as 5.6 mg cm−3 for 0.5% (w/v) the mucilage polymer, a specific surface area of 4 to 20 m2 g−1, high oil absorption capacity (23 g g−1), and prominent compressibility. The natural biopolymer technique leads to low cost and biocompatible functional lightweight materials with tunable properties (physicochemical and mechanical) and significant potential for applications as supporting or stimuli responsive materials, carriers, reactors, microwave- and electromagnetic radiation protective (absorbing)-materials, as well as in drug delivery and oil absorption

The cellular interactions of PEGylated gold nanoparticles : effect of PEGylation on cellular uptake and cytotoxicity

Poly(ethylene glycol) (PEG) is frequently used to coat various medical nanoparticles (NPs). As PEG is known to minimize NP interactions with biological specimens, the question remains whether PEGylated NPs are intrinsically less toxic or whether this is caused by reduced NP uptake. In the present work, the effect of gold NP PEGylation on uptake by three cell types is compared and evaluated the effect on cell viability, oxidative stress, cell morphology, and functionality using a multiparametric methodology. The data reveal that PEGylation affects cellular NP uptake in a cell-type-dependent manner and influences toxicity by different mechanisms. At similar intracellular NP numbers, PEGylated NPs are found to yield higher levels of cell death, mostly by induction of oxidative stress. These findings reveal that PEGylation significantly reduces NP uptake, but that at similar functional (= cell-associated) NP levels, non-PEGylated NPs are better tolerated by the cells

Versatile Route for Multifunctional Aerogels Including Flaxseed Mucilage and Nanocrystals

Preparation of low density monolithic and free-standing organic-inorganic hybrid aerogels of various properties is demonstrated using green chemistry from a biosafe natural source (flaxseed mucilage) and freeze-casting and subsequent freeze drying. Bio-aerogels, luminescent aerogels, and magneto-responsive aerogels are obtained by combination of the flaxseed mucilage with different types of nanoparticles. Moreover, the aerogels are investigated as possible drug release systems using curcumin as a model. Various characterization techniques like thermogravimetric analysis, nitrogen physisorption, electron microscopy, UV/Vis absorption, and emission spectroscopy, bulk density, and mechanical measurements, as well as in vitro release profile measurements, are employed to investigate the obtained materials. The flaxseed-inspired organic-inorganic hybrid aerogels exhibit ultra-low densities as low as 5.6 mg cm(-3) for 0.5% (w/v) the mucilage polymer, a specific surface area of 4 to 20 m(2) g(-1), high oil absorption capacity (23 g g(-1)), and prominent compressibility. The natural biopolymer technique leads to low cost and biocompatible functional lightweight materials with tunable properties (physicochemical and mechanical) and significant potential for applications as supporting or stimuli responsive materials, carriers, reactors, microwave- and electromagnetic radiation protective (absorbing)-materials, as well as in drug delivery and oil absorption

In depth characterisation of the biomolecular coronas of polymer coated inorganic nanoparticles with differential centrifugal sedimentation

Advances in nanofabrication methods have enabled the tailoring of new strategies towards the controlled production of nanoparticles with attractive applications in healthcare. In many cases, their characterisation remains a big challenge, particularly for small-sized functional nanoparticles of 5 nm diameter or smaller, where current particle sizing techniques struggle to provide the required sensitivity and accuracy. There is a clear need for the development of new reliable characterisation approaches for the physico-chemical characterisation of nanoparticles with significant accuracy, particularly for the analysis of the particles in the presence of complex biological fluids. Herein, we show that the Differential Centrifugal Sedimentation can be utilised as a high-precision tool for the reliable characterisation of functional nanoparticles of different materials. We report a method to correlate the sedimentation shift with the polymer and biomolecule adsorption on the nanoparticle surface, validating the developed core–shell model. We also highlight its limit when measuring nanoparticles of smaller size and the need to use several complementary methods when characterising nanoparticle corona complexes

Nanoparticles: Synthesis, Surface Modification and Functionalization for Biological and Environmental Applications

In addition to the type or nature of the nanoparticles (NPs) core, the surface of the obtained nanoparticles plays a crucial role and has great impact on the physicochemical properties of the nanoparticles which reflect in turn on the nanomaterials interactions (with the surrounding medium, biological systems and environment), functionalities and their possible applications. The general focus of this doctoral dissertation has been paid to the synthesis, controlled surface modification, functionalization, purification and characterization of different types of (plasmonic, semiconductor and magnetic) nanoparticles providing water soluble and highly colloidally stable nanoparticles proper for environmental and biological applications. Most of the as synthesized nanoparticles are inorganic particles (e.g. 5 nm Au NPs, 12 nm magnetic iron oxide NPs, 3 nm iron platinum NPs, 8 nm cobalt platinum NPs, CdSe/ZnS core/shell QDs of different sizes from 3-5 nm to 7 nm ZnO QDs) stabilized by hydrophobic organic molecules known as the surfactant or ligand which play an important role to control the shape and growth of the during the nanoparticles synthesis in addition to its role as stabilizing agents preventing the nanoparticles to be agglomerated. In case of water insoluble (hydrophobically capped) nanoparticles (not suitable for the biological applications), they were transformed from organic phase to aqueous environment using a very general protocol known as amphiphilic polymer coating which is based on the hydrophobic interaction between the hydrophobic ligands on the surface of the nanoparticles and the hydrophobic side chains of the used polymer. The polymer coating of originally organic-solvent soluble nanoparticles converts them to water soluble ones (thanks to the free carboxylate groups on surface) which have the ability to be further functionalized with extra functional and/or biologically active molecules of interest. The obtained polymer coated nanoparticles were purified and characterized using different techniques, such as agarose gel electrophoresis, size exclusion chromatography, UV-Vis spectroscopy, fluorescence spectroscopy (in case of fluorescent materials), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Monodisperse different types of polymer coated nanoparticles were obtained with a high quality and colloidal stability as inferred from their physicochemical properties such as narrow hydrodynamic diameter distribution and the negative surface charges expressed as zeta potential. Furthermore, the surface of some water soluble polymer coated nanoparticles was modified with different functionalities such as some fluorophores (e.g. Dy-495, DY-647 and rhodamine), polyethylene glycol, folic acid and methotrexate to obtain multifunctional nanoparticles that could be useful for a wide range of biological applications such as tracking, labeling and multimodal imaging and targeting drug delivery

The Cellular Interactions of PEGylated Gold Nanoparticles: Effect of PEGylation on Cellular Uptake and Cytotoxicity

Poly(ethylene glycol) (PEG) is frequently used to coat various medical nanoparticles (NPs). As PEG is known to minimize NP interactions with biological specimens, the question remains whether PEGylated NPs are intrinsically less toxic or whether this is caused by reduced NP uptake. In the present work, the effect of gold NP PEGylation on uptake by three cell types is compared and evaluated the effect on cell viability, oxidative stress, cell morphology, and functionality using a multiparametric methodology. The data reveal that PEGylation affects cellular NP uptake in a cell-type-dependent manner and influences toxicity by different mechanisms. At similar intracellular NP numbers, PEGylated NPs are found to yield higher levels of cell death, mostly by induction of oxidative stress. These findings reveal that PEGylation significantly reduces NP uptake, but that at similar functional (= cell-associated) NP levels, non-PEGylated NPs are better tolerated by the cells. Nanoparticle PEGylation influences cell interaction. PEGylation of gold nanoparticles is studied under both identical nanoparticle doses and similar intracellular nanoparticle concentrations. PEGylation is found to impede cell uptake in a cell-specific manner and impedes nanoparticle effects on cell morphology. However, PEGylation increases oxidative stress and does not always appear to be optimally suited for in vitro cell labeling. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.status: publishe

Evaluation of quantum dot cytotoxicity: interpretation of nanoparticle concentrations versus intracellular nanoparticle numbers

<p>While substantial progress has been achieved in the design of more biocompatible nanoparticles (NP), detailed data are required on the precise interactions of NPs and their environment for more reliable interpretation of toxicity results. Therefore, this study aims to investigate the interaction of two quantum dots (QDs) of the same core material CdSe/ZnS coated with two different amphiphilic polymers, with two well-established mammalian cell lines representing possible sites of QD accumulation. Results are linked to either extracellular QD concentrations (given dose) or cellular QD levels (number of internalized particles). In this study, QD internalization, effects on cellular homeostasis, and consequent inflammatory and cytoskeletal alterations caused by these QDs were explored. Fluorescence imaging techniques, including; image-based flow cytometry, confocal microscopy and high-content imaging with the InCell analyzer were used in a multiparametric methodology to evaluate cell viability, induction of oxidative stress, mitochondrial health, cell cytoskeletal functionality and changes in cellular morphology. Gene expression arrays were also carried out on 168 key genes involved in the cytoskeletal architecture and inflammatory pathway accompanied with the analysis of focal adhesions as key markers for actin-mediated signaling. Our results show distinct differences between the PMA and PTMAEMA-<i>stat</i>-PLMA coated QDs, which could mainly be attributed to differences in their cellular uptake levels. The toxicity profiles of both QD types changed drastically depending on whether effects were expressed in terms of given dose or internalized particles. Both QDs triggered alterations to important but different genes, most remarkably the up-regulation of tumor suppression and necrosis genes and the down regulation of angiogenesis and metastasis genes at sub-cytotoxic concentrations of these QDs.</p