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Patent Issued for Multifunctional Metal Nanoparticles Having a Polydopamine-Based Surface and Methods of Making and Using the Same

August 8, 2014



By a News Reporter-Staff News Editor at Drug Week -- A patent by the inventors Messersmith, Phillip B. (Clarendon Hills, IL); Black, IV, Kvar C. L. (Evanston, IL); Yi, Ji (Evanston, IL); Rivera, Jose G. (Waukegan, IL), filed on March 14, 2012, was published online on July 22, 2014, according to news reporting originating from Alexandria, Virginia, by NewsRx correspondents (see also Northwestern University).

Patent number 8784895 is assigned to Northwestern University (Evanston, IL).

The following quote was obtained by the news editors from the background information supplied by the inventors: "Metal nanoparticles (NPs) have a long history of use dating back to the 4.sup.th or 5.sup.th century B.C.E. The optical properties of conductive gold and silver NPs have been associated with the surface plasmon resonance (SPR) of metals, which when confined to small colloids, is referred to as the localized surface plasmon resonance (LSPR). This phenomenon, in which the free electrons oscillate collectively on the metal surface when irradiated with particular energies of light, causes wavelength dependent absorption and scattering of light and is the source of the colors associated with metal nanoparticles. The size, shape, and composition of the colloidal particles determines the energy of the SPRs, and therefore, control over the synthesis of metal NPs provides an ability to tune the optical properties of the nanometals contained therein.

"Since Turkevich et al. first described the synthesis of metal nanoparticles by reduction of cationic noble metal ions in solution (Discuss. Faraday Soc. 11(1951): 55), colloidal suspensions of various NP morphologies have been accomplished, including gold-silver alloys (Y. Sun et al., Analyst 128 (2003): 686-691), core-shell NPs (D. B. Wolfe et al., Langmiur 15 (1999): 2745), gold nanorods (NRs) (N. R. Jana et al., J. Phys. Chem. B 105(19) (2001): 4065-4067), silver nanosheets (J. Xie et al., ACS nano 1(5) (2008): 429-439, and gold nanocages (J. Chen et al., Nano Lett. 5(3) (2005): 473-477). Hybrid approaches such as silver-shell gold NR core NPs have also been employed (M. Lui et al., J. Phys. Chem. B 108 (2004): 5882-5888).

"Surface plasmon resonant metal nanoparticles have broad potential in medical diagnostic and therapeutic applications, due to their relative inertness, sub-100 nm size, unique electromagnetic properties, and strong optical tunability. Accordingly, metal NPs have attracted attention in the biomedical field. For example, linking DNA to gold NPs allows biological interactions to form assemblies of colloidal clusters that change the optical properties of the suspension (C. A. Mirkin et al., Nature 382 (1996): 607-609), which can be detected for diagnostic purposes. Because SPRs enhance many optical processes, including Raman scattering, fluorescence, and two-photon excited luminescence, gold NPs have been used in optical diagnostics (K. Aslan et al., Current Opinion in Chemical Biology 9 (2005): 538-544) and as contrast agents for bioimaging (I. H. El-Sayed et al., Nano Letters 5(5) (2005): 829-834; K. C. Black et al., Mol. Imaging. 7(1) (2008): 50-57). When gold NPs absorb light energy, they also release heat, potentially making them useful in photothermal therapy applications targeting cancer (T. B. Huff et al, Nanomedicine 2(1) (2007): 125-132) and bacterial cells (S. E. Norman et al., Nano letters 8(1) (2008): 302-306.

"However, the use of metal NPs for medical diagnosis and treatment is limited, because NPs cannot be fully integrated into the biological realm without tailored control over their surface chemistry. Biomolecules and cells interact through a multitude of chemical interactions and physical forces which have not evolved in the presence of noble metals, and therefore interactions between biological systems and metal NPs are non-specific. In order to realize the full biomedical potential of gold nanoparticles, the nanoparticles must interact specifically with biological matter, including cell surface components. Furthermore, nanoparticle aggregation and nonspecific interactions with molecular and cellular constituents of the biological system must be minimized. Thus, there is a need in the art for metal nanoparticles that can be readily modified to precisely control their electromagnetic and biofunctional properties."

In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "The disclosure encompasses novel metal nanoparticles having polydopamine polymerized onto the nanoparticle surface. In some embodiments, the surface is modified further in a variety of ways. Non-limiting examples of the function of such further modifications include modulating toxicity, controlling the conversion of light energy to heat energy, inhibiting non-specific interactions, increasing solubility in physiological conditions, providing pro-apoptotic function, providing specific targeting, and providing growth factor pathway inhibition.

"Accordingly, in a first aspect, the disclosure encompasses nanoparticles that includes a metallic core having a length along each axis of from 1 to 100 nanometers, and a polydopamine coating disposed on at least part of the surface of the metallic core. In some embodiments, the metallic core is a nanorod having a substantially cylindrical shape. In some embodiments, the polydopamine coating is disposed on the entire surface of the metallic core. In some embodiments, the metallic core includes gold, and optionally, may consist essentially of gold.

"The polydopamine coating may be modified in a number of ways, depending on the desired function of the nanoparticles. For example, in some embodiments the coating may further include silver. In some embodiments, the coating may further include iron oxide. In some embodiments, the nanoparticles further include one or more polymers, polysaccharides sugar-containing peptoids, pharmaceutical agents, antibodies, polyethylene glycol, or functionalized polyethylene glycol bound to the coating. Optionally, one or more of the bound antibodies is an anti-cancer cell surface receptor antibody or an anti-bacterial surface antibody. Optionally, one or more of the bound pharmaceutical agents is an anti-cancer agent or an anti-microbial agent.

"In a second aspect, the disclosure encompasses a method of making the nanoparticles described above. The method includes the step of contacting a metallic core having a length along each axis of from 1 to 100 nanometers with an alkaline solution comprising dopamine. This step results in the formation of a polydopamine coating on the surface of the metallic core. In some embodiments, the metallic core is a nanorod having a substantially cylindrical shape. In some embodiments, the metallic core consists essentially of gold.

"In a third aspect, the disclosure encompasses a method for treating cancer. The method includes the step of administering to a patient having cancer cells one or more of the nanoparticles that are described above. In some embodiments, the metallic core consists essentially of gold, and one or more anti-cancer cell surface receptor antibodies are bound to the polydopamine coating of the nanoparticles. The antibodies cause the nanoparticles to target the cancer cells. A non-limiting example of an antibody that could be bound to the coating of the nanoparticles to target cancer cells is an anti-epithelial growth factor receptor (EGFR) antibody.

"In some embodiments, the nanoparticles may further include an additional anti-cancer agent bound to the polydopamine coating. A non-limiting example of such an anti-cancer agent is a proteasome inhibitor, such as bortezomib.

"In some embodiments, the method further includes the step of exposing the nanoparticles to light. Upon such exposure, the nanoparticles heat up, and the resulting photothermal therapy differentially kills the targeted cells.

"In a fourth aspect, the disclosure encompasses a method for treating a bacterial infection. The method includes the step of administering to a patient infected with bacteria one or more of the nanoparticles described above that include a metallic core consisting essentially of gold and an anti-bacterial surface antibody bound to the polydopamine coating. The nanoparticles then target the bacteria that is the source of the infection.

"Optionally, the anti-bacterial surface antibody is an anti-lipoteichoic acid antibody or an anti-endotoxin antibody. In some embodiments, the polydopamine coating further incorporates a layer of silver. In some embodiments, the method further includes the step of exposing the nanoparticles to light.

"In a fifth aspect, the disclosure encompasses a method for imaging cancer or bacterial cells. The method includes the steps of contacting cancer or bacterial cells with one or more of the nanoparticles described above, wherein the metallic core consists essentially of gold and wherein the nanoparticles include an anti-cancer cell surface receptor antibody or an anti-bacterial surface antibody bound to the polydopamine coating. The antibody functions as a targeting agent so that the nanoparticles target the cancer or bacterial cells.

"The method also includes the step of detecting the location of the one or more nanoparticles. Optionally, this step may be performed using bright field microscopy, optical coherence tomography, or 2-photon confocal microscopy. In some embodiments, the nanoparticle coating further comprises iron oxide, and the step of detecting the location of the one or more nanoparticles is performed using magnetic-based imaging.

"Further objects, features and advantages of the invention will be apparent from the following detailed description when taken in conjunction with the accompanying drawings."

URL and more information on this patent, see: Messersmith, Phillip B.; Black, IV, Kvar C. L.; Yi, Ji; Rivera, Jose G.. Multifunctional Metal Nanoparticles Having a Polydopamine-Based Surface and Methods of Making and Using the Same. U.S. Patent Number 8784895, filed March 14, 2012, and published online on July 22, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8784895.PN.&OS=PN/8784895RS=PN/8784895

Keywords for this news article include: Antibacterial, Antibodies, Antimicrobials, Cancer, Therapy, Oncology, Immunology, Nanoparticle, Blood Proteins, Nanotechnology, Immunoglobulins, Membrane Proteins, Emerging Technologies, Cell Surface Receptors, Northwestern University, Bacterial Infections and Mycoses.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Drug Week


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