Liposomes hold great potential in anti-
cancer drug delivery and the targeting treatment of
tumors. However, the clinical therapeutic efficacy of
liposomes is still limited by the complexity of tumor microenvironment (TME) and the insufficient accumulation in
tumor sites. Meanwhile, the application of
cholesterol and
polyethylene glycol (PEG), which are usually used to prolong the blood circulation and stabilize the structure of
liposomes respectively, has been questioned due to various disadvantages. Herein, we developed a
ginsenoside Rh2-based multifunctional
liposome system (Rh2-lipo) to effectively address these challenges once for all. Different with the conventional 'wooden'
liposomes, Rh2-lipo is a much more brilliant carrier with multiple functions. In Rh2-lipo, both
cholesterol and PEG were substituted by Rh2, which works as membrane stabilizer, long-circulating stealther, active targeting
ligand, and
chemotherapy adjuvant at the same time. Firstly, Rh2 could keep the stability of
liposomes and avoid the shortcomings caused by
cholesterol. Secondly, Rh2-lipo showed a specifically prolonged circulation behavior in the blood. Thirdly, the accumulation of the
liposomes in the
tumor was significantly enhanced by the interaction of
glucose transporter of
tumor cells with Rh2. Fourth, Rh2-lipo could remodel the structure and reverse the immunosuppressive environment in TME. When tested in a 4T1
breast carcinoma xenograft model, the
paclitaxel-loaded Rh2-lipo realized high efficient
tumor growth suppression. Therefore, Rh2-lipo not only innovatively challenges the position of
cholesterol as a
liposome component, but also provides another innovative potential system with multiple functions for anti-
cancer drug delivery.