Nanoporous silica-based protocells at multiple scales for designs of life and nanomedicine

Abstract

Various protocell models have been constructed de novo with the bottom-up approach. Here we describe a silica-based protocell composed of a nanoporous amorphous silica core encapsulated within a lipid bilayer built by self-assembly that provides for independent definition of cell interior and the surface membrane. In this review, we will first describe the essential features of this architecture and then summarize the current development of silica-based protocells at both micro- and nanoscale with diverse functionalities. As the structure of the silica is relatively static, silica-core protocells do not have the ability to change shape, but their interior structure provides a highly crowded and, in some cases, authentic scaffold upon which biomolecular components and systems could be reconstituted. In basic research, the larger protocells based on precise silica replicas of cells could be developed into geometrically realistic bioreactor platforms to enable cellular functions like coupled biochemical reactions, while in translational research smaller protocells based on mesoporous silica nanoparticles are being developed for targeted nanomedicine. Ultimately we see two different motivations for protocell research and development: (1) to emulate life in order to understand it; and (2) to use biomimicry to engineer desired cellular interactions.

Figure 1

(A) Fusion of small unilamellar vesicles on nanoporous silica cell replicas and other silica particles forms protocells; (B) The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed the VDAC1 protein (arrow) from different samples. VDAC1 successfully incorporated into the DOPC or Soy Lecithin-coated protocells (Lane 9 and 10) while the supernatant of the centrifuged protocells contained no VDAC1 (Lane 7 and 8). Most VDAC1 proteins precipitated when detergent Lauryldimethylamine-oxide (LDAO) was removed from the lipid-detergent-protein mixture (Lane 3 and 4). Original SUVs before protein incorporation had no VDAC1 (Lane 5 and 6).

Figure 2

(A) The design of the FRET-based Shp2 biosensor; (B) The protocells visualized with coated DOPC membranes with 1% Texas Red- DHPE and loaded fluorescent Shp2 biosensor inside the silica cell replicas; (C) In the presence of loaded PDGFR kinase, the FRET of the Shp2 biosensor inside silica cells increased upon ATP addition.

Figure 3

The cartoon depicts the nanoporous silica-based protocell for drug delivery.