Ligand-targeted delivery of drug molecules to various types of tumor cells remains a major challenge in precision medicine. Inspired by the secretion process and natural cargo delivery functions of natural exosomes, biomimetic synthetic strategies are exploited to prepare biofunctionalized liposome-like nanovesicles (BLNs) that can artificially display a wide variety of targeting protein/peptide ligands and directly encapsulate medical agents for enhanced drug delivery. As a proof of concept, researchers from Xiamen University developed genetically engineered BLNs, which display human epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, respectively, to target two types of tumor cells. Notably, in comparison to synthetic liposomes covalently coupled with hEGF, it is demonstrated in this work that biosynthetically displayed hEGF ligands on BLNs possess higher biological activities and targeting capabilities. Additionally, treatments with doxorubicin-loaded BLNs displaying Affibody ligands exhibit much better antitumor therapeutic outcomes than clinically approved liposomal doxorubicin (Doxil) in HER2-overexpressing BT474 tumor xenograft models. These data suggest that BLN is suitable as a potent surrogate for conventional proteoliposomes or immunoliposomes as a result of excellent targeting capacities and facile production of BLNs.
Schematic illustration of biofunctionalized liposome-like nanovesicle (BLN) preparation
a) The genes of targeted protein ligands (hEGF or Affibody) were genetically engineered and then transfected into cells to express the modified targeting ligands on cell surface. b) Expressed protein ligands were further transported to Golgi body via signal peptide-mediated protein trafficking route. c) Transport vesicles carrying ligands from the Golgi body fused with the plasma membrane, thus presenting targeting proteins on cellular surface. d) With sodium deoxycholate entrapped into plasma membrane, ligand-presenting giant plasma membrane vesicles begin to bud from cell surface in a manner similar to secretion process of exosomes. e) After incubation of giant plasma membrane vesicles with drugs and surfactants, ultrasonic vibrating facilitated to encapsulate photosensitizer (ICG) or chemotherapeutic agent (Dox) into uniform nanoscaled BLNs. f) Drug-loaded BLNs exhibit excellent ligand-mediated affinity to the overexpressing receptors (EGFR or HER2) on tumor surface.