Real-time bioimaging of hyaluronic acid derivatives using quantum dots for biopharmaceutical delivery applications

摘要

Hyaluronic acid (HA), which has been used for various medical applications, is a biocompatible, biodegradable, and linear polysaccharide in the body. In this work, real-time bioimaging of HA derivatives was carried out using quantum dots (QDot) for target specific and long acting delivery applications of protein, peptide, and nucleotide therapeutics. In vitro bioimaging of HA-QDot conjugates successfully visualized the target specific delivery of HA derivatives to B16F1 cells with HA receptors by HA receptor mediated endocytosis, which reflects the feasibility of HA derivatives for intracellular delivery of biopharmaceuticals, especially nucleotide therapeutics. Furthermore, according to in vivo real-time bioimaging, HA-QDot conjugates with 35 mol% HA modification were mainly accumulated in the liver, while those with 68 mol% HA modification were evenly distributed to the tissues in the mice. Accordingly, slightly modified HA derivatives were used for target-specific delivery of biopharmaceuticals for the treatment of liver diseases and highly modified HA derivatives were used for long acting conjugation of peptide and protein therapeutics. These HA-based biopharmaceutical delivery systems can be exploited for further clinical development.