KR-102961398-B1 - POLYMER NANOPARTICLE HAVING LYMPH NODE MIGRATION ABILITY, MANUFACTURING METHOD THEREOF, AND USE THEREOF

Abstract

The present invention relates to polymer nanoparticles having lymph node migration ability, and more specifically, provides polymer nanoparticles for bioimaging characterized by comprising polydopamine nanoparticles; and a near-infrared fluorescent dye bound to the surface of said polydopamine nanoparticles, and having lymph node migration ability, a method for manufacturing the same, and uses the same. The polymer nanoparticles for bioimaging according to the present invention can provide nanoparticles with improved lymph node mobility by controlling the average size of polydopamine nanoparticles through pH control.

Inventors

• 심가용
• 강성택

Assignees

• 숭실대학교 산학협력단

Dates

Publication Date

20260508

Application Date

20230627

Claims (10)

1. Polydopamine nanoparticles; and The near-infrared fluorescent dye bound to the surface of the above polydopamine nanoparticles includes indocyanine green, and The above polydopamine nanoparticles were polymerized in a basic solution with a pH of 10 to 11, and then acid Polymer nanoparticles for bioimaging, characterized by improved lymph node migration ability and metastatic lymph node detection ability, prepared by processing and mixing with an indocyanine green solution at pH 2 to 3 to form polydopamine nanoparticles combined with indocyanine green having an average particle size of 75 to 85 nm.
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4. A contrast agent composition for lymph node detection comprising polymer nanoparticles according to claim 1.
5. In Article 4, The above contrast agent composition is, A contrast agent composition for detecting lymph nodes, characterized by being for detecting lymph nodes that have metastasized to cancer.
6. A drug delivery system composition for cancer treatment comprising polymer nanoparticles according to claim 1.
7. A step of dissolving dopamine salt in a solvent and then treating it with a base; A step of stirring and centrifuging the above base-treated dopamine salt solution to obtain polydopamine nanoparticle pellets; A step of washing the obtained nanoparticle pellets and suspending them in a solvent; and The method includes the step of acid-treating the above suspension, adding an indocyanine green solution, stirring, and centrifuging to obtain polydopamine nanoparticles bound to indocyanine green. The above base treatment step is performed by adding a basic solution to the dopamine salt solution and titrating the pH to 10 to 11, and The step of obtaining the polydopamine nanoparticles bound to the indocyanine green is performed by acid-treating the suspension to adjust the pH to 2 to 3, and mixing the pH-adjusted suspension and the indocyanine green solution in a volume ratio of 1: (0.1 to 1) to obtain polydopamine nanoparticles bound to the indocyanine green having an average particle size of 75 to 85 nm. A method for manufacturing polymer nanoparticles for bioimaging, characterized by improved lymph node migration ability and metastatic lymph node detection ability.
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Description

Polymer nanoparticles having lymph node migration ability, manufacturing method thereof, and use thereof The present invention relates to polymer nanoparticles having lymph node migration ability, and more specifically, to polydopamine nanoparticles combined with indocyanine green, a method for manufacturing the same, and uses the same. Lymph nodes are nodule-shaped sacs located in the middle of lymphatic vessels spread throughout the body. They play a role in defending the body by producing lymphocytes that perform immune functions and removing foreign substances, such as bacteria, that have invaded the lymphatic vessels. Lymph nodes are distributed throughout the body along lymphatic vessels and are the points where lymphatic vessels and lymphatic pathways connect. Lymph nodes are particularly concentrated in areas such as the neck and armpits, where immune responses occur. However, paradoxically, lymph nodes can also serve as a pathway for cancer metastasis. In conventional imaging diagnostic methods such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) used to non-invasively detect metastatic lymph nodes, the primary criterion for determining lymph node metastasis is an increase in lymph node size. However, due to limitations such as the possibility of metastasis in normal-sized lymph nodes and the difficulty in differentiating them from enlarged benign proliferative lymph nodes, satisfactory results in terms of sensitivity, specificity, and accuracy have not been achieved. Nanoparticles are being applied in various fields, including nano-electronic fusion technology, bioimaging technology, and medicine. Generally, since the accumulation and drainage of nanoparticles in the lymphatic system vary depending on their size, nanoparticle technology with suitable sizes and shapes is required for the detection of metastatic lymph nodes. Figure 1 shows a schematic diagram of a nanoparticle (hereinafter PN/ICG) in which indocyanine green (ICG) is bonded to the surface of a polydopamine nanoparticle (PN) according to one embodiment of the present invention. Figure 2 shows the results of measuring the size of four different PN/ICGs with different pH values according to one embodiment of the present invention and several comparative examples using dynamic light scattering. Figure 3 is a transmission electron microscope (TEM) image of four PN/ICGs with different pH values. Figure 4 shows the results of observing migration to lymph nodes using an in vivo imaging system after administering PN/ICG to the hind paw pads of Balb/c mice. Figure 5 is a photograph of lymph nodes collected and visually observed after in vivo imaging of a Balb/c mouse administered PN/ICG to the right hind paw. Figure 6 shows the results observed using an in vivo imaging system after administering PN/ICG to the forefoot of a tumor animal model exhibiting luciferase activity. Figure 7 shows the results of administering PN/ICG to the forefoot of a tumor animal model exhibiting luciferase activity, observing the results with an in vivo imaging system, and then measuring the fluorescence intensity of the dissected animal with an in vivo imaging system. Figure 8 shows the results of measuring the detection ability of PN/ICG on metastatic lymph nodes using an LED-based surface microscope. The present invention will be described in detail below. The inventors completed the present invention by confirming that, since accumulation and drainage in the lymphatic system differ depending on the size of the nanoparticles, polydopamine nanoparticles of an appropriate size for detecting lymph node migration and metastatic lymph nodes can be manufactured through pH control. The present invention provides a polymer nanoparticle for bioimaging having lymph node migration ability. More specifically, the polymer nanoparticles may comprise polydopamine nanoparticles; and a near-infrared fluorescent dye bound to the surface of the polydopamine nanoparticles. In this specification, "polydopamine" refers to a protein produced by mussels living in the sea, which has adhesive properties in water and low cytotoxicity , and possesses excellent biocompatibility that does not cause adverse effects in the body. Its precursor, dopamine ( C8H11NO2 ), is an organic compound of the catecholamine family, and is one of the neurohormones and neurotransmitters found in the nervous system secreted by the central nervous system or hypothalamus of various animals, and has the property of spontaneously undergoing a polymerization reaction under basic conditions to become polydopamine. Preferably, the polymer nanoparticles may be polymerized in a basic solution with a pH of 9 to 11 and have an average particle size of 70 to 700 nm, and more preferably, polymerized in a basic solution with a pH of 10 to 11 and have an average particle size of 70 to 90 nm, but are not limited thereto. According to one experimental example of the present invention, it can be conf