부산대학교 도서관

Background: The tumor-targeting ability and pH-sensitive properties of intelligent drug delivery systems are crucial for effective drug delivery and anti-tumor therapy. Methods: In this study, sHA-DOX/HA-GA mixed micelles were designed with the following properties: sulfated hyaluronic acid (sHA) was synthesized to block cell migration by inhibiting HAase; sHA-DOX conjugates were synthesized via pH-sensitive hydrazone bond to realize DOX-sensitive release. The introduction of HA-GA conjugate could improve active-targeting ability and cellular uptake. Results: The results showed that the mixed micelles possessed a nearly spherical shape, nanoscale particle size (217.70[+ or -]0.89 nm), narrow size distribution (PDI=0.07[+ or -]0.04), negative zeta potential (-31.87[+ or -]0.61 mV) and pH-dependent DOX release. In addition, the sHA-DOX /HA-GA micelles exhibited concentration-dependent cytotoxicities against liver carcinoma cells (HepG2) and HeLa cells, and were shown to be effectively taken up by HepG2 cells by confocal microscopy analysis. Furthermore, the in vivo anti-tumor study showed that mixed micelles had a superior anti-tumor effect compared to that of free DOX. Further evidence obtained from the hematoxylin--eosin staining and immunohistochemistry analysis also demonstrated that sHA-DOX/HA-GA exhibited stronger tumor inhibition and lower systemic toxicity than free DOX. Conclusion: The sHA-DOX/HA-GA mixed micelles could be a potential drug delivery system for anti-hepatoma therapy. Keywords: hyaluronic acid, glycyrrhetinic acid, hepatoma-targeting, pH-sensitive, micelles, anti-tumor therapy
Introduction Liver cancer is one of the most common malignancies, with steadily increasing incidence globally. It has become the fourth leading cause of cancer-related deaths. (1,2) Traditional chemotherapy is one [...]