It has been reported that the cellular uptake of nanoparticles is morphologically dependent. Experimental verification on this topic requires a good control over the uniformity of various nanoparticle morphologies made of the same materials. In the past, we were able to self-assemble disk-like bicelles and oblate vesicles in a lipid mixture composed of a zwitterionic long-chain 1,2-dihexadecanoyl-sn-3-phosphocholine (DPPC), a zwitterionic short chain1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) doped with small quantities of charged long-chain 1,2-dihexahecanoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (DPPG) and a PEGylated lipid, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). The structures of bicelles and vesicles are confirmed by small angle neutron scattering through appropriate model fitting. It shows that the cellular uptake of bicelles is 3 ~ 5 folds of that of the vesicles. Moreover, four uptake pathways have been examined for both nanoparticles, i.e., clathrine-mediated, caveolae-mediated, macropinocytosis and microtubules, respectively. The result shows that vesicles only take the former two mechanisms, while bicelles take all four pathways, to be internalized in the cells. This understanding furthers our knowledge of the cell-nanoparticle interaction which may advance the design for drug delivery nanocarriers.

Cellular uptake mechanisms as controlled by nanostructures of a lipid mixture: Comparison between bicelles and vesicles

249th National Meeting (2015)

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