Lipid nanoparticles (LNPs) have become the cornerstone of nucleic acid delivery, yet challenges remain in achieving targeted biodistribution, avoiding immune activation, and expanding routes of administration. Inspired by the functional diversity of extracellular vesicles (EVs), we have developed a novel platform of whole-cell lipid nanoparticles (WCLNPs), formulated using lipidomes extracted from different mammalian cell types.
Each WCLNP variant reflects the lipid composition of its parent cell, conferring unique membrane properties that influence in vivo biodistribution, cellular tropism, and immune compatibility. We created a library of WCLNPs and characterized them in terms of size, charge, encapsulation efficiency. Using fluorescent and nucleic acid cargos, we systematically evaluated their biodistribution following intravenous injection in mice.
Importantly, WCLNPs maintain the tunability of synthetic LNPs, allowing the incorporation of ionizable or cationic lipids to further modulate delivery efficiency. The platform shows potential across multiple therapeutic areas, including gene delivery, immunotherapy, and tissue-specific drug targeting.
Our results demonstrate that biologically sourced lipidomes can endow nanoparticles with programmable delivery profiles, representing a new direction at the interface of synthetic nanomedicine and natural vesicle biology.