Mohammed Ibrahim Shukoor

Au@MnO Nanoflowers: Hybrid Nanocomposites for Selective Dual Functionalization and Imaging

Recently, the development of hybrid nanostructures consisting of various materials has attracted considerable interest. The assembly of different nanomaterials with specific optical, magnetic, or electronic properties to multicomponent composites can change and even enhance the properties of the individual constituents. Specifically tuning the structure and interface interactions within the nanocomposites has resulted in novel platforms of materials that may lead the way to various future technologies, such as synchronous biolabeling, protein separation and detection, heterogeneous catalysis, and multimodal imaging in biomedicine. Of the various kinds of nanomaterials, gold nanorods show an unusually high polarizability at optical frequencies arising from the excitation of localized surface-plasmon resonances (LSPRs). Furthermore, gold nanorods have promising therapeutic properties as hyperthermal agents because the local temperature around the gold nanorods can be increased by laser illumination through the tunable surface plasmon bands in the near infrared (NIR) region. Using NIR radiation for hyperthermal therapy is beneficial because of the low absorption and low scattering by blood and tissue in this spectral range. Magnetic nanoparticles constitute another major class of nanomaterials that have attracted much research effort over the past decades. In particular, exchange-coupled magnetic nanocomposites, such as antiferromagnetic/ferromagnetic core–shell nanoparticles, such as MnO/Mn3O4, have magnetic properties that are quite different from those of the individual components. Concerning biomedical applications, superparamagnetic nanoparticles are attractive as contrast agents for magnetic resonance imaging (MRI). The majority of nanoparticles that have been investigated in this field comprise iron oxides (Fe3O4, g-Fe2O3), which are known to shorten the transverse (or spin–spin) relaxation time T2. [11] Recently, manganese oxide nanoparticles (MnO NPs) have been shown to be interesting candidates as contrast agents for shortening of the longitudinal (or spin-lattice) relaxation time T1. [12] Consequently, a nanoparticulate system containing both an optically active plasmonic gold unit and a magnetically active MnO component would be advantageous for simultaneous optical and MRI detection. Although considerable research efforts have been put into the chemical design of suitable surface ligands, one of the major obstacles for biocompatible applications remains the lack of surface addressability. Therefore, a nanocomposite made up of individually addressable Au and MnO domains offers two functional surfaces for the attachment of different kinds of molecules, thus increasing both diagnostic and therapeutic potential. Furthermore, the size of either of the two components can be varied to optimize the magnetic and optical properties. Herein we present the successful synthesis of Au@MnO nanocomposites consisting of both paramagnetic MnO NPs and Au crystallites followed by separate surface functionalization of both domains with fluorescent ligands. Scheme 1 depicts a functionalized Au@MnO nanoflower with selective attachment of catechol anchors to the metal oxide petals and thiol anchors to the gold core. The nanoflowers were synthesized by decomposition of manganese acetylacetonate [Mn(acac)2] in diphenyl ether in the presence of preformed Au NPs (“seeds”), with oleic acid and oleylamine as surfactants, following a similar procedure for the preparation of Au@Fe3O4 heteroparticles by Sun et al. [15] The [*] T. D. Schladt, Dr. M. I. Shukoor, K. Schneider, Dr. M. N. Tahir, O. K hler, Prof. Dr. W. Tremel Institut f r Anorganische Chemie und Analytische Chemie Johannes-Gutenberg-Universit t Duesbergweg 10–14, 55099 Mainz (Germany) Fax: (+49)6131-39-25605 E-mail: tremel@uni-mainz.de

Superparamagnetic γ-Fe2O3 nanoparticles with tailored functionality for protein separation

Polymer coated superparamagnetic γ-Fe2O3 nanoparticles were derivatized with a synthetic double-stranded RNA [poly(IC)], a known allosteric activator of the latent (2-5)A synthetase, to separate a single 35 kDa protein from a crude extract which cross reacted with antibodies raised against the sponge enzyme.

CpG-DNA loaded multifunctional MnO nanoshuttles for TLR9-specific cellular cargo delivery, selective immune-activation and MRI

Initiation of pathways that lead to a proliferation and chemoresistance by Toll-like receptors (TLRs) are an important factor in cancer progression. Multifunctional magnetic nanoparticles equipped with a pathogen-derived ligand (CpG) functioning as TLR agonists were used to show the impact of immune activation on human HNSCC (head and neck squamous cell carcinoma) cells. The response of human cancer cells to TLR signaling is linked to tumor biology. The magnetic MnO nanoparticles were coated with a multifunctional polymer, displaying no cytotoxicity and being able to enter cells while carrying foreign DNA (unmethylated CpG) to recognize intracellular TLR9. Both the particle and the nucleic acid were tagged with fluorescent markers for simultaneous visualization inside the cell. Cell and animal studies show that the multimodal nanoparticles used as a TLR carrier system allow monitoring simultaneously nanoparticle cellular trafficking and transport by optical and MRI imaging.

Engineered Multifunctional Nanotools for Biological Applications

Smart multifunctional magnetic nanoparticles are popular candidates for several biological applications owing to their intrinsic magnetic property and diverse applications that range from rare protein separation and biomedical utilization to cancer therapy and diagnostics. A universal protocol, for the development of such nanocarriers, is highly desirable for scientists with different backgrounds so that custom-made multifunctional nanoparticles can be developed to address their needs, among which are the superparamagnetic iron oxide and manganese oxide nanoparticles that are synthesized through high temperature decomposition reactions. However, an interface is needed to present these inorganic materials to biomolecules to enhance their application for different biological use. This compatibility is achieved by introducing a class of multifunctional copolymers. Magnetic nanoparticles are elaborately decorated with copolymers that carry three principle functionalities as follows: (1) dopamine moieties for surface anchorage of metal oxides; (2) dyes for optical detection; and (3) a large variety of functional molecules such as amines or carboxylates for conjugation of various biomolecules (i.e., proteins, nucleic acids, enzymes, etc.). These copolymers, in combination with nanoparticles, serve as a tool box that results in engineered nanotools with customized modifications and functionalities for applications in fields ranging from proteomics -bioseparation to tumor therapy.

Cell Specific Targeting of Multifunctional γ-Fe 2 O 3 Nanoparticles Through Surface Binding of dsDNA

The immobilization of polyinosinic-polycytidylic acid [poly(IC)] on a-Fe 2 O 3 maghemite nanoparticles via the phosphor-amidate route using a multifunctional polymer is reported. The dsRNA coupled nanoparticles were used to visualize the Toll-like (TLR3) receptors at the cell surface. The presence of TLR3 was demonstrated independently in the Caki-1 cell line by RT-PCR and immunostaining techniques