Nanoparticle drug delivery vehicles require a coating that is robust, biocompatible, and facilitates long circulation times in the biofluid but must efficiently uncloak to release the drug cargo upon reaching its target site. A lipid bilayer coated mesoporous silica nanoparticle, called the protocell, has been shown to release its contents of small molecule cargo upon lowering to acidic pH (~ 5) thus providing a route for cargo delivery via the endosomal pathway. The mechanism of cargo release, however, is currently unknown. We recently found that lipid bilayers on glass reorganize their structure upon lowering of solution pH to result in the formation of large pores. The pores form rapidly (within seconds) spanning out to several microns in diameter with irregular shape. Pore formation was further found to be general for PC lipids in either the fluid phase (e.g., POPC, DOPC) or the gel phase (e.g., DPPC), although the latter forms smaller pores (sub- micron). Through molecular models we find that a bilayer membrane under tension forms pores that are stabilized in the presence of lipids with positive spontaneous curvature. Using a novel wedge-shaped lipid prepared in our lab we were able to show the formation of large stable pores, thus verifying the latter portion of the modeling prediction. The generation of membrane tension through pH change of a supported lipid bilayer on silica as the driving force for membrane pore formation will be discussed.

pH-dependent behavior of lipid bilayer coatings on mesoporous silica nanoparticles

253rd National Meeting (2017)

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