Identification and construction of a novel biomimetic delivery system of paclitaxel and its targeting therapy for cancer

Paclitaxel (PTX) is among the first-line therapeutic agents against diverse malignancies. However, problems still exist concerning its poor water-solubility, multidrug resistance, lack of specific targeting ability and severe toxic effects, and these issues are far from fully resolved despite the various PTX formulations available on the market, e.g. the gold standard, PTX albumin nanoparticles Abraxane ® , 1 and PTX liposomes Lipusu ® . Some studies that try to solve the multiple problems faced by chemotherapy drug delivery, however, fell into the prevailing trap of overcomplicated formulation design which sacrifices the druggability. 2 To better reconcile this paradox, a novel glycosylated liposomal PTX was designed, inspired by the cytomembrane glycosyls with important roles in maintaining both membrane structure and physiological functions, 3 , 4 such as enhancing membrane stability, evading immunological clearance, and recognizing corresponding receptors. Ginsenosides, as natural amphiphilic molecules, are structurally similar to cholesterol, contain glycosyl moieties, and are easily obtainable. Thus, we adopted ginsenoside as a substitute for cholesterol in liposomes, with its hydrophobic region inserted into the lipid bilayer, and its glycosyl exposed on the liposomal surface providing biomimetic functions. This ginsenoside-anchored liposome was named ginposome, and the paclitaxel-loaded ginposome (G-PTX) system exhibited enhanced encapsulation and stability, reduced monocyte phagocytosis, and active targeting towards tumor cells by recognizing their overexpressed glucose transporters. In addition, the ginsenoside could also serve as chemotherapy adjuvant due to its inherent pharmacological functions. 5