Bacterial components as naturally inspired nano-carriers for drug/gene delivery and immunization: Set the bugs to work?

Abstract

Drug delivery is a rapidly growing area of research motivated by the nanotechnology revolution, the ideal of personalized medicine, and the desire to reduce the side effects of toxic anti-cancer drugs. Amongst a bewildering array of different nanostructures and nanocarriers, those examples that are fundamentally bio-inspired and derived from natural sources are particularly preferred. Delivery of vaccines is also an active area of research in this field. Bacterial cells and their components that have been used for drug delivery, include the crystalline cell-surface layer known as "S-layer", bacterial ghosts, bacterial outer membrane vesicles, and bacterial products or derivatives (e.g. spores, polymers, and magnetic nanoparticles). Considering the origin of these components from potentially pathogenic microorganisms, it is not surprising that they have been applied for vaccines and immunization. The present review critically summarizes their applications focusing on their advantages for delivery of drugs, genes, and vaccines.

Keywords: Bacterial components; Bacterial ghosts; Bacterial polymers; Drug delivery system; Endospores; Immunization, S-layer; Nanomedicine.

Figure 1

Subcellular morphology of A. migulanus. (a) cell wall consisting of outer S-layer protein (OSLP), peptidoglycan (PG), inner S-layer protein (ISLP) and cell membrane (CM), (b) localization of Gramicidin S containing granules like polyhydroxyalkanoates (PHA), (c) size estimation of the granules, (d) cells that are covered with S-layer proteins are found to be intact in the SEM, whereas those cells that have shed their S-layer proteins are seen to be disrupted and have release their granules into the environment. (e) Two types of granules are distributed over the silicon support when the S-layer protein was washed off and the neighboring cells got ruptured (Berditsch et al., 2017). no permission required

Figure 2

S-layer functionalized emulsomes showing: (A) naked emulsomes structure (B) emulsomes coated with S-layer protein/ wtSbsB (C) S-layer protein/ rSbs B coated emulsomes. Reprinted with permission from Wiley (Ucisik et al., 2013).

Figure 3

There are several methods to incorporate antigens in BGs. A) through fusion between TA with MBP, B) TA using the gene III signal sequence, C) binding to TA which attached to E′, L′ or E′/L′-anchoring or binding to E′-FXa-StrpA membrane anchors if biotinylated. (TA = Teichoic acid) (Langemann et al., 2010). no permission required

Figure 4

V. alginolyticus BGs under TEM, (a) 30,000× scanning electron micrograph including transmembrane tunnels. (b) 4,000× transmission electron micrograph (Cao et al., 2018) no permission required

Figure 5

Schematic illustration of use of an anti-HER2 specific affibody on OMVs loaded with siRNA. Reprinted with permission from American Chemical Society (Gujrati et al., 2014).

Figure 6

Prodrug-converting enzyme gene (cytosine deaminase) was inserted into a plasmid which was transformed into Clostridium. Spores produced by the bacteria were collected, prepared and directly injected into a tumor-bearing animal. The spores spread in the body, but germination only occurred in hypoxic areas of the tumor. After 1–2 weeks (the time required for colonization), the prodrug (5-fluorocytosine) was administered. The conversion of the prodrug into the active drug (5-fluorouracil) caused tumor regression (Minton, 2003). Reprinted with permission from Nature Reviews Microbiology.

Figure 7

Chemical structures of some bacterial-based biopolymers

Scheme 1

Schematic illustration of bacteria and bacterial components