UC San Diego

Self-assembling lipopeptide nanocarriers have emerged as one of the most powerful delivery vehicles, providing unique opportunities to transport therapeutic drugs. In efforts to improve target specificity, such carriers are functionalized with integrin-binding motifs (such as RGD peptide sequences), enhancing cellular uptake via ligand-receptor interactions. However, common approaches for the preparation of the desired structures require complex synthetic routes to covalently conjugate the peptide ligands to the lipid fragments. It would be thus valuable to develop a straightforward methodology to construct biocompatible vehicles that can efficiently deliver functional cargos to live cells. Herein, we describe a new class of nanocarrier systems constituted by self-assembling lipopeptides conjugated with specific integrin-binding motifs. The approach takes advantage of chemoselective and non-enzymatic methods to synthesize functional lipopeptides, which spontaneously self-assemble into micron-sized vesicles. The straightforward construction of our model systems, jointly with their robustness, biocompatibility and simplicity, highlights their relevant use as carriers for the enhanced cellular uptake of fluorescently labeled biomacromolecules (Texas Red-Dextran) and therapeutic agents (doxorubicin) via receptor-mediated endocytosis pathway.