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. Here, as a proof of concept, genetically engineered BLNs, which display human
epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, are developed to, respectively, 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.