Bioimaging for Targeted Delivery of Hyaluronic Acid Derivatives to the Livers in Cirrhotic Mice Using Quantum Dots

Abstract

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.

Nonlinear optical properties of near-infrared region Ag2S quantum dots pumped by nanosecond laser pulses

“…The transmission pulse is 10.5 ns for Ag 2 S QDs, and 21.08 ns for CHCl 3 . The transmission pulse of nanostructure particles is much shorter than that of the laser pulse.…”

Target specific systemic delivery of TGF-β siRNA/(PEI-SS)-g-HA complex for the treatment of liver cirrhosis

“…The secretion of hepatitis C virus (HCV), the leading cause of liver cirrhosis, is reported to be highly dependent on lipoproteins [23]. In accordance with the target specific systemic delivery of HAQDot with a modification less than 25 mol% to the liver [14], siApoB/(PEI-SS)-g-HA complex was effectively delivered to the liver after tail-vein injection to Balb/c mice. The gene silencing efficiency increased up to ca.…”

“…As a drug delivery carrier, HA has several advantages including the negligible non-specific interaction with serum components due to the polyanionic characteristics [10] and the highly efficient target specific delivery to the liver tissues with HA receptors [11e13]. According to our previous study, quantum dot labeled HA (HA-QDot) molecules were target specifically delivered to the liver and remained much longer in a cirrhotic liver than a normal liver [14]. Interestingly, the hepatocellular distribution study revealed that a large amount of HA-QDots were also delivered to HSCs as well as LSECs [14].…”

“…According to our previous study, quantum dot labeled HA (HA-QDot) molecules were target specifically delivered to the liver and remained much longer in a cirrhotic liver than a normal liver [14]. Interestingly, the hepatocellular distribution study revealed that a large amount of HA-QDots were also delivered to HSCs as well as LSECs [14]. In addition, we previously reported the effective local tumor treatment with VEGF siRNA complexed with reducible polyethyleneimine (PEI-SS)-b-HA conjugates [15].…”

Quantum dots, lighting up the research and development of nanomedicine

“…Based on this result, they further compared the retention behavior of the conjugates in a normal and diseased liver. 75 Interestingly, it revealed that the clearance of conjugates was relatively slow in a cirrhotic liver. Furthermore, immunofluorescence and flow cytometric analyses of dissected liver tissues showed the target-specific delivery of HA derivatives to liver sinusoidal endothelial cells and hepatic stellate cells.…”