1. Field of the Invention
The present invention relates to a nanoparticle coated with ligand introduced with a long hydrophobic chain and a method for preparing the same.
2. Description of the Related Art
Nanoparticle refers to a particle whose size is in the range of several nm to several hundred nm. Nanoparticle technology accounts for an important part of nanotechnology as a core technology backing a high-tech industry for the 21st century.
The nanoparticle has particular physical properties—e.g. photic, electrical, and magnetic properties—unlike other bulk particle and thus the nanoparticle produces excellent performances in various applications including electromagnetism, optics, catalysts, sensors, storage, drug delivery system, tissue engineering, diagnostic reagents, and many others. Since the nanoparticle is used in such a wide range of application fields, the technology for preparing the nanoparticle is emerging as a promising technology for the next generation.
Nanoparticle has a growing presence in the medical and pharmaceutical fields, in particular, because the market for the nanoparticle was expected to increase from USD$3.39 billion in 2007 to USD$26 billion in 2012 in the fields, creating a high added value. In addition, the technology for delivering the nanoparticle selectively to a specific tissue, which uses the particular properties of the nanoparticle, is applicable to the body and also usefully applicable to the fields of in-vitro research including tissue staining and cell binding analysis.
Introducing diverse ligands onto the surface of a nanoparticle gives specificity to the nanoparticle for a particular tissue. In addition, introducing two or more different ligands gives the nanoparticle specificity of binding to two or more targets, and thereby enables a specific in-vivo or in-vitro binding to a particular receptor and antigen and provides various detection methods by binding several probes selected from among radioisotopes, optically active materials, and magnetic materials to the nanoparticle.
As the detection methods based on the various conventional detection mechanisms have been widely developed, the nanoparticle probes that may apply several methods and detect various targets simultaneously have been developing.
For example, there has been a report of constructing a bispecific antibody for both epidermal growth factor receptor (EGFR) and cyclin-dependent kinase inhibitor 1 (CDKI) at the same time, attaching first to the surface of a cell and then going into the cell, and attaching to CDK in the cell (Cornelissen B, et al., Cancer Biother Radiopharm, 24:163-173, 2009). Also, it has been reported that the bispecific engineered antibody for fragment antigen-binding (Fab) and histamine-succinyl-glycine (HSG) fragment is applied to 2 step imaging (Sharkey R M, et al., Cancer Biother Radiopharm, 25:1-12, 2010).
Korean Patent No. 2009-0044293 discloses a nanoparticle for bio-imaging having both bioaffinity and target orientation, which is prepared by partially reforming a part of the surface of the hydrophobic nanoparticle to the hydrophilic one, introducing a desired functional molecule to the hydrophilic group, preparing a functional nanoparticle presenting overall hydrophobicity, and converting the rest part of the nanoparticle surface into the hydrophilic one. In the meantime, Korean Patent No. 2008-0037734 discloses a quantum dot for biocompatible molecular imaging, whose surface is composed of cadmium selenite core and zinc sulfide shell and is attached with cysteamine and water-soluble monosaccharide.
However, the conventional nanoparticle presents hydrophobic property immediately after the preparation and therefore cannot be applied as is to biological or pharmaceutical research conducted mostly under water-soluble condition. Thus, an additional process of introducing residual hydrophilic groups is necessary for the preparation. Moreover, since a nanoparticle is recognized as a foreign substance in the body, it migrates to the reticuloendothelial system immediately after the administration into the body. To prevent this, an additional process of coating polymer such as PEG onto the nanoparticle is required.
In the meantime, such chemical reaction as covalent bond has been mainly performed to introduce diverse ligands to the hydrophilically treated nanoparticle. However, efficiency can deteriorate due to many factors of this chemical reaction including the reaction temperature, pH, presence of impurities, difference of concentration between various reagents, and light. In particular, the error can be severer as the bonding reaction progresses between two or more and thus the variables can be complicated, making the prediction of the reaction harder and reproducibility deteriorate.
Accordingly, the inventors of the present invention have completed the present invention, after finding the method of introducing various ligands to a hydrophobic nanoparticle easily by synthesizing a substance in which a ligand is conjugated with one long alkyl chain and coating the substance onto the hydrophobic nanoparticle through non-covalent bond, in the course of researching on the method of introducing various kinds of ligands, which can be simple and highly recurring for various kinds of hydrophobic nanoparticles.