Synthetic immunosurveillance systems: nanodevices to monitor physiological events

Abstract

The field of nanotechnology has recently seen vast advancements in its applications for therapeutic strategy. This technological revolution has led way to nanomedicine, which spurred the development of clever drug delivery designs and ingenious nanovehicles for the monitoring of cellular events in vivo. The clinical implementations of this technology are innumerable and have demonstrated utility as diagnostic tools and fortifying machineries for the mammalian immune system. Recently engineered viral vectors and multi-subunit packaging RNAs have verified stable enough for long-term existence in the physiological environment and therefore reveal unique potential as artificial immunosurveillance devices. Physiological and pathological events recorded by nanodevices could help develop "biocatalogs" of patients' infection history, frequency of disease, and much more. In this article, we introduce a novel design concept for a multilayer synthetic immune network parallel to the natural immune system; an artificial network of continuously patrolling nanodevices incorporated in the blood and lymphatic systems, and adapted for molecular event recording, anomaly detection, drug delivery, and gene silencing. We also aim to discuss the approaches and advances recently reported in nanomedicine, especially as it pertains to promising viral and RNA-based nanovehicles and their prospective applications for the development of a synthetic immunosurveillance system (SIS). Alternative suggestions and limitations of these technologies are also discussed.

Keywords: Drug-delivery; Nanomedicine; Nanovirology; Theranostics; Viral vectors.

Fig. 1.

Nano-scaled elements with potential for nanovector assembly.(A) Isotype structures and formulas of three (1R,2R)-(−)-1,2-Cyclohexanediamino-N,N’-bis(3,5-di-t-butylsalicylidene)cobalt(II)-based organometallic chemicals with physiologically-favorable stability for nanovector assembly. (B) Electrostatic potential of two capsid proteins from plant-infecting and animal-infecting viruses with unique prospective as nanovehicle platforms. (Left) Cowpea Mosaic Virus (CPMV) capsid protein subunit; and (Right) Nanoporouscrystals of Chicken Embryo Lethal Orphan (CELO) Adenovirus Major Coat Protein. Blue and red colors indicate positive and negative electrostatic potential, respectively. Protein ID obtained from Protein Data Bank (PDB).

Fig. 2.

Illustration of an active synthetic immunosurveillance system (SIS) in an aging patient. (Top to bottom) Molecular event recording, artificial immune surveillance, and artificial immune defense represent the three pillars of SIS. Involution offsets T-cell production and leads to malignant growth-stimulated inflammatory response. Patrolling viral-based nanovehicles are equipped with RNA motors and pH-controlled nanochromophores to detect inflammatory signatures. The vehicles then migrate to cellular compartments via the lymphatic and blood networks to release functional transcripts, siRNAs, therapeutic aptamers, or chemotoxic nanoemulsion droplets. Probed transcripts are then released by the nanovehicles and dispersed into the cellular milieu to monitor molecular events and catalog disease frequency.

Fig. 3.

One arm of SIS will utilize lipid-based vesicles and viral vectors to carry artificial immune surveillance. A carrier cell engineered to produce viral capsids produces large amounts of viral-based vectors. Antibodies-bound nano piezoelectrodes are packaged inside lipid-based nano-vesicles and introduced into the bloodstream to be phagocytosed by a carrier cell. While in the cytoplasm, vesicles unleash nano piezoelectrodes, which bind specific viral coating receptors, resulting in the assembly of functional piezoelectrode-equipped nanovehicles inside the carrier cell. The assembled probed nanodevices are then released into the bloodstream to patrol and be incorporate inside blood and lymphatic networks.

Fig. 4.

Workflow of promising nanovehicles and their respective advantages and challenges in a SIS. (Clockwise) Viral and bacterial-based vectors perhaps represent the most promising arm of nanovehicle technology. Liposomes, solid lipids, and oligonucleotide based vectors could be readily incorporated into the immune defense arm of SIS. As well studied nanotechnologies, organometallic-based vectors provide a potent therapeutic component to nanovehicle designs. Dendrimers, functional monomers, and micelles are rising as some of the most stable and cell-specific nanovectors in vivo. Tocopherols, from which vitamin E is derived, have shown promise as immune surveillance vehicles.