In vivo real-time bioimaging of hyaluronic acid derivatives using quantum dots.
The effect of chemical modification of hyaluronic acid (HA) on its distribution throughout the body was successfully visualized in nude mice through real-time bioimaging using quantum dots (QDots). Adipic acid dihydrazide modified HA (HA-ADH) was synthesized and conjugated with QDots having carboxyl terminal ligands activated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide. The formation of HA-QDot conjugates could be confirmed by gel permeation chromatography, fluorometry, transmission electron microscopy, and zeta-size analysis. According to the real-time bioimaging of HA-QDot conjugates after subcutaneous injection to nude mice, the fluorescence of HA-QDot conjugates with a near infrared wavelength of 800 nm could be detected up to 2 months, whereas that with an emission wavelength of 655 nm disappeared almost completely within 5 days. The results can be ascribed to the fact that near-infrared light has a high penetration depth of about 5-6 cm in the body compared to that of about 7-10 mm for visible light. Thereby, using QDots with a near-infrared emission wavelength of 800 nm, the distribution of HA-QDot conjugates throughout the body was bioimaged in real-time after their tail-vein injection into nude mice. HA-QDot conjugates with 35 mol% ADH content maintaining enough binding sites for HA receptors were mainly accumulated in the liver, while those with 68 mol% ADH content losing much of HA characteristics were evenly distributed to the tissues in the body. The results are well matched with the fact that HA receptors are abundantly present in the liver with a high specificity to HA molecules.
Kim
Jiseok
J
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang 790-784, Republic of Korea.
Kim
Ki Su
KS
Jiang
Ge
G
Kang
Hyungu
H
Kim
Sungjee
S
Kim
Byung-Soo
BS
Park
Moon Hyang
MH
Hahn
Sei Kwang
SK
D000818:Animals; D002240:Carbohydrate Sequence; D002850:Chromatography, Gel; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011199:Potentiometry; D011789:Quantum Theory
D006820:Hyaluronic Acid