Environment-responsive hyaluronic acid nanoparticles
View Patent ↗The present invention relates to glucose-responsive hyaluronic acid nanoparticles having boronic acid compounds chemically bonded thereto, and a composition including the same. When the nanoparticles according to the present invention are used, cancer may be diagnosed and treated using a cancer cell-specific biological mechanism, without the use of existing contrast agents and anticancer agents which have the problem of toxicity.
1. A hyaluronic acid complex comprising a hyaluronic acid-boronic acid repeating unit in which a boronic acid compound is bound to a carboxyl group of a repeating unit represented by the following Formula 1
wherein the boronic acid compound in the hyaluronic acid-boronic acid repeating unit is bound to a hyaluronic acid repeating unit via an amide bond by means of a diamine compound serving as a linker, and
wherein the diamide compound is ethylenediamine, butylenediamine, hexamethylenediamine, pentaethylenehexamine, or 1,5-diamino-2-methylpentane.
2. The hyaluronic acid complex of claim 1 , wherein a content of the hyaluronic acid-boronic acid repeating unit is in a range of 15 to 55 parts by mol, based on 100 parts by mol of the hyaluronic acid complex.
3. The hyaluronic acid complex of claim 1 , wherein the boronic acid compound is phenylboronic acid.
4. The hyaluronic acid complex of claim 3 , wherein the phenylboronic acid comprises one or more selected from the group consisting of N-(4-phenylboronic) succinamic acid, 3-carboxybenzenebenzoic acid, 4-carboxypyridine-3-benzoic acid, and (3-aminomethylphenyl) benzoic acid chloride.
5. The hyaluronic acid complex of claim 1 , wherein the hyaluronic acid complex comprises the hyaluronic acid repeating unit represented by Formula 1 together with the hyaluronic acid-boronic acid repeating unit.
6. A plurality of glucose-responsive nanoparticles that are spherical particles having a hydrophobic core, wherein the hyaluronic acid complex defined in claim 1 is self-aggregated to form the spherical particles.
7. The glucose-responsive nanoparticles of claim 6 , wherein the nanoparticles have an average diameter of 200 nm to 400 nm.
8. The glucose-responsive nanoparticles of claim 6 , further comprising a fluorescent signal material with which spherical particles are chemically labeled or which is physically loaded into a hydrophobic core.
9. The glucose-responsive nanoparticles of claim 8 , wherein the fluorescent signal material is chlorine 6 (Ce6) or cyanine 5.5 (Cy5.5).
10. A pharmaceutical composition for diagnosing or treating liver cancer, comprising the glucose-responsive nanoparticles defined in claim 6 .
11. The pharmaceutical composition of claim 10 , which inhibits aerobic glycolytic metabolism of cancer cells by using glucose responsivity.