Bioimaging for targeted delivery of hyaluronic Acid derivatives to the livers in cirrhotic mice using quantum dots.
Liver fibrosis or cirrhosis is one of the representative liver diseases with a high morbidity and mortality worldwide. Over the past decades, many kinds of antifibrotic compounds have been investigated in vitro and in vivo for the treatment of liver cirrhosis. In this work, real-time bioimaging of hyaluronic acid (HA) derivatives was carried out using quantum dots (QDots) to assess the possibility of HA derivatives as target-specific drug delivery carriers for the treatment of liver diseases. HA-QDot conjugates with an HA modification degree of about 22 mol % was synthesized by amide bond formation between carboxyl groups of QDots and amine groups of adipic acid dihydrazide modified HA (HA-ADH). According to in vitro cell culture tests, HA-QDot conjugates were taken up more to the cells causing chronic liver diseases such as hepatic stellate cells (HSC-T6) and hepatoma cells (HepG2) than normal hepatocytes (FL83B). After tail-vein injection, HA-QDot conjugates were target-specific, being delivered to the cirrhotic liver with a slow clearance longer than 8 days. Furthermore, immunofluorescence and flow cytometric analyses of dissected liver tissues revealed the target-specific delivery of HA derivatives to liver sinusoidal endothelial cells (LSEC) and HSC. The results were thought to reflect the feasibility of HA derivatives as novel drug delivery carriers for the treatment of various chronic liver diseases including hepatitis, liver cirrhosis, and liver cancer.
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea.
Ki Su
KS
Kim
Wonhee
W
Hur
Sang-Jun
SJ
Park
Sung Woo
SW
Hong
Jung Eun
JE
Choi
Eun Ji
EJ
Goh
Seung Kew
SK
Yoon
Sei Kwang
SK
Hahn
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology*; D008422:Materials Testing; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D045663:Quantum Dots
D004337:Drug Carriers; D006820:Hyaluronic Acid