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.

Membrane-forming phospholipids provide essential functions to living organisms, rendering them as one of the ideal candidates to explore the evolutionary origins of compartmentalization. However, current model systems to generate membranes, have been mainly focused on working with long chain amphiphiles containing phospho-head groups, which require a biochemically complex machinery unlikely to have been achieved in the early stages of life. Therefore, it highlights the significance of novel systems of membrane synthesis prior to the development of integral membrane proteins in early protocells. To better understand the plausible mechanisms of early lipid synthesis and membrane compartmentalization, strategies of in situ formation membranes may be developed using simple molecular building blocks, such as soluble proteins, simple peptides, and short acyl chains. This summary includes construction of amphiphilic lipids by using a chemoselective reaction to demonstrate how artificial cells may potentially mimic the properties of natural biological membranes and thus, spontaneously create biocompatible membranes.