The biophysical properties of lipid vesicles are important for their stability and integrity, key parameters that control
the performance when these vesicles are used for drug delivery. The lipid vesicle properties are determined by the
composition and arrangement of lipids used to form the vesicle. However, the symmetric structure of the lipid
bilayer limits the tailoring of their biophysical and biochemical properties. Here, we present a novel approach
for the design of asymmetric lipid vesicles with arbitrary lipid compositions. Compared to symmetric lipid vesicles,
we find that asymmetric lipid vesicles lead to higher cell uptake and mRNA transfection while having a reduced cell
cytotoxicity. We also show that the lipid vesicle properties for a given lipid composition can be tailored by
asymmetrically tethering polysaccharides to the membrane. Overall, asymmetric lipid vesicles provide the
means to fine-tune and tailor drug delivery carriers to enable the next generation of disease treatment and
vaccine technology.
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