Hyaluronic acid-coated shikonin liposomes for the treatment of triple-negative breast cancer via targeting tumor cells and amplification of oxidative stress

Abstract

Triple-negative breast cancer (TNBC) is an aggressive phenotype that lacks effective therapies. Amplification of oxidative stress is reportedly effective against tumors. Shikonin (SHK) is a potent natural antitumor product that regulates oxidative stress. In the current study, hyaluronic acid-coated SHK liposomes (HA-SHK-Lip) were prepared for the treatment of TNBC. The prepared HA-SHK-Lip displayed high drug encapsulation efficiency and slow drug release. The antitumor effects of HA-SHK-Lip were evaluated both in vitro and in vivo. Our in vitro cytotoxicity study indicated that HA-SHK-Lip effectively inhibited the proliferation of MDA-MB-231 cells. Cellular uptake of HA-SHK-Lip via the CD44 receptor-mediated endocytosis pathway was much higher than that of free SHK and SHK-Lip. Further research showed that HA-SHK- could significantly enhanced the production of intracellular reactive oxygen species (ROS) and reduced intracellular glutathione (GSH). HA-SHK-Lip exerted a much better antitumor effect than free SHK and SHK-Lip in BALB/C mice bearing MDA-MB-231 tumors. These results suggested that HA-SHK-Lip could be an effective therapeutic strategy for combating TNBC via targeting tumor cells and enhancing cellular oxidative stress.