Gold Half-Shell Coated Hyaluronic Acid-Doxorubicin Conjugate Micelles for Theranostic Applications

Abstract

Theranostic systems have been widely investigated for application in the diagnostic therapy of cancers. In this work, hyaluronic acid (HA)-doxorubicin (DOX) conjugate was successfully synthesized by the amide bond formation between amine groups of DOX and carboxylic groups of HA activated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide. The H-1 nuclear magnetic resonance (NMR) and gel permeation chromatographic (GPC) analyses confirmed the successful synthesis of HA-DOX conjugates. HA-DOX conjugates self-assembled to micelle-like nanoparticles in aqueous solution. In vitro anti-proliferation tests of cancer cells confirmed the anti-tumor effect of HA-DOX conjugate micelles. For further application, the micelles were coated with a gold (Au) half-shell by the thermal vapor deposition method, which might contribute to prolonging the residence time in the body with a versatile surface modification on the Au surface. TEM analysis confirmed the successful Au coating on HA-DOX conjugate micelles with a thickness of 15 nm. The Au half-shell-coated HADOX conjugate micelles might be successfully exploited for cancer theranostic applications such as chemotherapy, hyperthermia, and bioimaging.