Microbial Fabricated Nanosystems: Applications in Drug Delivery and Targeting

Abstract

The emergence of nanosystems for different biomedical and drug delivery applications has drawn the attention of researchers worldwide. The likeness of microorganisms including bacteria, yeast, algae, fungi, and even viruses toward metals is well-known. Higher tolerance to toxic metals has opened up new avenues of designing microbial fabricated nanomaterials. Their synthesis, characterization and applications in bioremediation, biomineralization, and as a chelating agent has been well-documented and reviewed. Further, these materials, due to their ability to get functionalized, can also be used as theranostics i.e., both therapeutic as well as diagnostic agents in a single unit. Current article attempts to focus particularly on the application of such microbially derived nanoformulations as a drug delivery and targeting agent. Besides metal-based nanoparticles, there is enough evidence wherein nanoparticles have been formulated using only the organic component of microorganisms. Enzymes, peptides, polysaccharides, polyhydroxyalkanoate (PHA), poly-(amino acids) are amongst the most used biomolecules for guiding crystal growth and as a capping/reducing agent in the fabrication of nanoparticles. This has promulgated the idea of complete green chemistry biosynthesis of nano-organics that are most sought after in terms of their biocompatibility and bioavailability.

Keywords: biomineralization; drug delivery; fabrication; microbes; nano-organics; nanomaterial.

Figure 1

Schematic diagram of microbial fabricated nanosystems and their application in drug delivery and targeting. (A) Biosynthesis of inorganic metal nanoparticles and biopolymeric nanoparticles. The nanoparticles can be functionalized with variety of peptides, polynucleotides, amino acids, targeting moiety. (B) Application of nanoparticles in drug and gene delivery via active and passive mode of targeting and in high quality diagnostic techniques as contrast agents. PEI Polyethyleneimine, EPS ExoPolySaccharides, CPP Cell Penetrating Peptide, PEG Polyethylene Glycol, PHA PolyHydroxyAlkanoates, mAb Monoclonal Antibody, EPR Enhanced Permeability, and Retention.

Figure 2

Magnetotactic bacteria (MTB) and drug delivery applications. (A) MTB as a multimodal photoacoustic, photothermal, and photomechanical contrast agent for single cell diagnostic and therapy (Nima et al., 2019). (B) Conceptual diagram depicting a single microrobot, the Artificial Bacterial Flagellum ABF, enhancing mass transport of NPs at the vessel -tissue interface (left), and swarms of MTB generating convective flow to improve mass transport (right). ECM ExtraCellularMatrix (Schuerle et al., 2019). (C) Drug delivery using physiological limitation of MTB under hyperthermia radiation (Alsaiari et al., 2016).

Figure 3

Application of Diatom based NPs in drug delivery. (A) Dual drug chemotherapy approach using Diatomaceous SiNP and bacterial magnetic nanowires. The drugs are released specifically in the colon region in pH responsive manner and under magnetic field (Maher et al., 2017). (B) The drugs were encapsulated in Diatomaceous Earth Microparticles (DEMP) either in siliceous core or in β-CD and Adamantane (β-CD:Ad) micelles. Matrix MetalloProteinases-2 (MMP-2) specific peptide substrate was used as a linker between DEMPs core and βCD:Ad shell for stimuli responsive drug release into tumor tissue (Kabir et al., 2020).

Figure 4

Application of viruses, bacteria, and yeast cells in drug delivery and targeting. (A) RNA phage VLP as scaffold for foreign epitopes or encapsulating immunostimulating adjuvants (CpG) in vaccine delivery, drug or gene delivery and as bioimaging agents for MRI and PET based diagnosis (Pumpens et al., 2016). (B) Active targeting of a biosynthesized peptide CopA3 surface conjugated and ginsenoside compound K (CK) loaded gold nanoparticles (GNP-CK-CopA3). The particles, once internalized in macrophages, efficiently suppressed expression of pro-inflammatory cytokines through inhibition of NF-κB and MAPK signaling pathways (Liu et al., 2020). (C) Biosynthesis of HydroxyAPatite (HAP) nanoscaffold inside yeast cell for dual responsive drug delivery against tumor (Ma et al., 2018). VLP Virus Like Particles, FA Folic Acid, PDDA Poly- (Diallyl Dimethyl Ammonium chloride).