Heterodimeric core-shell nanoparticle in which raman-active molecules are located at a binding portion of a nanoparticle heterodimer, use thereof, and method for preparing same

Patent metadata

Field	Value
Publication number	US-2016266104-A1
Application number	US-201615069063-A
Country	US
Kind code	A1
Filing date	Mar 14, 2016
Priority date	May 7, 2008
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present invention relates to a nanoparticle heterodimer in which Raman-active molecules are located at a binding portion of the nanoparticle heterodimer, and more particularly, to a core-shell nanoparticle heterodimer comprising: a gold or silver core having a surface to which oligonucleotides are bonded; and a gold or silver shell covering the core. In addition, the present invention relates to the core-shell nanoparticle dimer, to a method for preparing same, and to the use thereof.

First claim

1 . A dimeric nanostructure, comprising two nanoparticles, with a Raman active molecule localized at a junction therebetween, each nanoparticle consisting of a gold or silver core with oligonucleotides attached to the surface thereof, and a gold or silver shell sheathing the core, wherein
the oligonucleotides in each nanoparticle are attached at one terminus to a surface of the core while being partially exposed to the outside of the shell, the oligonucleotides attached to the surface of each nanoparticle comprises a protecting oligonucleotide and a target-capturing oligonucleotide, the target-capturing oligonucleotides attached to the surface of the respective nanoparticles are hybridized directly with each other when they are complementary to each other or with a target oligonucleotide to form a dimeric nanostructure, and the target-capturing oligonucleotide on either nanoparticle is modified with the Raman active molecule.

2 . The dimeric nanostructure according to claim 1 , wherein the protecting oligonucleotide and the target-capturing oligonucleotide are attached via a surface-bound functional group selected from the group consisting of thiol group, amine group and alcohol group to the surface.

3 . The dimeric nanostructure according to claim 2 , wherein the oligonucleotide is offset by a spacer sequence from the surface-bound functional group.

4 . The dimeric nanostructure according to claim 1 , being selected from a group consisting of:
i) a dimeric nanostructure comprising two nanoparticles, each consisting of a gold core and a silver shell, ii) a dimeric nanostructure comprising two nanoparticles, each consisting of a silver core and a gold shell, iii) a dimeric nanostructure comprising two nanoparticles, each consisting of a gold core and a gold shell, iv) a dimeric nanostructure comprising two nanoparticles, each consisting of a silver core and a silver shell, and v) a dimeric nanostructure comprising two nanoparticles, one consisting of a gold core and a silver shell and the other consisting of a silver core and a gold shell.

5 . The dimeric nanostructure according to claim 1 , wherein the shell ranges in thickness from 1 to 300 nm.

6 . The dimeric nanostructure according to claim 1 , wherein the Raman active molecule is selected from a group consisting of FAM, Dabcyl, TRIT (tetramethyl rhodamine isothiol), NBD (7-nitrobenz-2-1,3-diazole), Texas Red dye, phthalic acid, terephthalic acid, isophthalic acid, cresyl fast violet, cresyl blue violet, brilliant cresyl blue, para-aminobenzoic acid, erythrosine, biotin, digoxigenin, 5-carboxy-4′,5′-dichloro-2′,7′-dimethoxy, fluorescein, 5-carboxy-2′,4′,5′,7′-tetrachlorofluorescein, 5-carboxyfluorescein, 5-carboxyrhodamine, 6-carboxyrhodamine, 6-carboxytetramethyl aminophthalocyanine, azomethine, cyanine, xanthine, succinylfluorescein, aminoacridine, quantum dots, carbone nanotubes, carbon allotropes, cyanide, thiol, chlorine, bromine, methyl, phosphorus, sulfur, cyanine dyes (Cy3, Cy3.5, Cy5), and rhodamine.

7 . The dimeric nanostructure according to claim 1 , wherein the Raman active molecule is an organic fluorescent molecule.

8 . The dimeric nanostructure according to claim 1 , being functionalized at a surface thereof or a surface of the core with a probe molecule capable of recognizing an analyte to be analyzed.

9 . The dimeric nanostructure according to claim 8 , wherein the analyte to be analyzed is selected from the group consisting of amino acids, peptides, polypeptides, proteins, glycoproteins, lipoproteins, nucleosides, nucleotides, oligonucleotides, nucleic acids, saccharides, carbohydrates, oligosaccharides, polysaccharides, fatty acids, lipids, hormones, metabolites, cytokines, chemokines, receptors, neurotransmitters, antigens, allergens, antibodies, substrates, co-factors, inhibitors, drugs, pharmaceutical substances, nutrients, prions, toxins, toxic substances, explosive substances, pesticides, chemical weapon agents, biologically noxious agents, radioactive isotopes, vitamins, heterocyclic aromatic compounds, oncogenic agents, mutagenic factors, anesthetics, amphetamine, barbiturate, hallucinogens, wastes, and contaminants.

10 . The dimeric nanostructure according to claim 8 , wherein the probe molecule is selected from the group consisting of antibodies, antibody fragments, soluble proteins, ligand proteins, enzymes, inhibitor proteins, cell-adhesion proteins, oligonucleotides, polynucleotides, nucleic acids, and aptamers.

11 . The dimeric nanostructure according to claim 1 , being entirely coated with an inorganic substance.

12 . The dimeric nanostructure according to claim 11 , wherein the inorganic substance is silica.

13 . A method for constructing the dimeric nanostructure of claim 1 , comprising:
1) synthesizing core A and core B, respectively, the core A having a protecting oligonucleotide and a target-capturing oligonucleotide which are bound to a surface thereof, the core B having a protecting oligonucleotide and a target-capturing oligonucleotide modified at one terminus with a Raman active molecule which is bound to a surface thereof; 2) hybridizing the core A and the core B with a target oligonucleotide to form a dimeric structure; and 3) introducing a shell on each of the core A and the core B.

14 . The method according to claim 13 , wherein the step 1 further comprises the step of
separating nanoparticles only which the target-capturing oligonucleotide is bound to in the core A and core B by hybridizing with magnetic microparticles having complementary sequence of the target-capturing oligonucleotide of core A and core B.

15 . The method according to claim 13 , wherein the introduction of the shell is achieved by reacting the core with a shell precursor in the presence of a reducing agent and a stabilizer.

16 . A method for detecting an analyte, comprising:
1) preparing the dimeric nanostructure of claim 9 , which has a surface of the dimeric nanostructure or the core functionalized with a probe molecule capable of detecting an analyte; 2) exposing the dimeric nanostructure to a sample containing at least one analyte; and 3) detecting and identifying the analyte by laser excitation and Raman spectroscopy.

17 . A dimeric nanostructure comprising:
a probe-A nanoparticle comprising:
a probe-A core;
a probe-A shell around the probe A core;
a probe-A protecting oligonucleotide attached to the probe-A core; and
a probe-A target capturing oligonucleotide attached to the probe-A core;
a probe-B nanoparticle comprising:
a probe-B core;
a probe-B shell around the probe B core;
a probe-B protecting oligonucleotide attached to the probe-B core; and
a probe-B target capturing oligonucleotide attached to the probe-B core; and
a Raman active molecule attached to at least one of the probe-A target capturing oligonucleotide and/or the probe-B target capturing oligonucleotide, wherein the probe-A nanoparticle and the probe-B nanoparticleare bridged together to form the dimeric nanostructure via complementary nucleotide sections of the probe-A target capturing oligonucleotide and the probe-B target capturing oligonucleotide.

18 . A dimer of Au/Ag core-shell composites,
each Au/Ag core-shell composite comprising an Au nanoparticle as a core; Ag layer as a shell surrounding the Au nanoparticle; and an oligonucleotide, of which one end is bonded to Au particle, via functional group or the spacer molecule having the functional group, and which is partially exposed to the outside of the shell; wherein Au/Ag core-shell composite having oli

Assignees

• Korea Res Inst Chemical Tech
• Univ Seoul Nat R & Db Found

Inventors

• Suh Yung Doug
• Nam Jwa Min
• Lim Dong Kwon

Classifications

• C12Q1/6816

  characterised by the detection means (C12Q1/6804 takes precedence) · CPC title

• G01N33/582

  with fluorescent label · CPC title

• G01N33/54346 Primary

  Nanoparticles · CPC title

• C12Q1/6825

  Nucleic acid detection involving sensors · CPC title

• G01N33/553

  Metal or metal coated · CPC title