Nanovex -Model Exosomes -Extracellular Vesicles
Exosomes are extracellular vesicles of natural origin that are produced by all cell types in the range of 40 to 160 nm. They have a key role in cell-to-cell communication and have been proved to be powerful tools in diagnosis and therapeutics. Their basic structure is very similar to liposomes, consisting of double lipid which is a slice of cell membrane and an aqueous based core which will be a part of cell plasma. For this reason, exosomes are rich in biological molecules, containing transmembrane proteins and receptors in their surface, as well as comprising nucleic acids, amino acids, metabolites, and other molecules within.
Exosomes then, act as delivery agents, for different biological purposes:
- Genetic expression regulation
- Survival and proliferation signalling
- Angiogenesis and wound healing stimulation
- Waste management
- Immunity triggering and balance
- Receptor ligand specific signalling
- Apoptosis control
- Cellular differentiation
- Indication of cellular migration and metastasis
- Metabolic programming
As mentioned above, exosomes are produced by all types of cells, and are formed by the endogenic pathway. The cell membrane folds inward, in a process called invagination, forming a lipid vesicle: the endosome. Then, inside the cell, macromolecules as proteins and genetic material are incorporated into the endosome, again by invagination, creating multiple exosomes. Finally, the endosome membrane fuses with the cell membrane to release these vesicles to be received by other cells.
Natural exosomes are very difficult to obtain and require expensive and strict purification and analytical procedures. For this reason, multiple technologies have been developed to synthesize extracellular vesicles very similar to exosomes.
Synthetic exosomes are outstanding drug carriers since they resemble cellular communication mechanisms. However, unlike natural exosomes, size and composition can be easily controlled and scalable for its use in preclinical or clinical settings. Since the assembly process can be monitored, it results in the formation of “clean”, well-characterized drug delivery systems. To date, exosomes have been used in many studies for tissue regeneration, delivery of drugs and genes, and diagnosis of diseases.
Natural exosomes produced endogenously by cells present some limitations such as homogeneity, expensive and difficult isolation as well as poor targeting specificity. For application in the clinical field, loading of exosomes with pharmaceuticals and targeting are required. For those reasons, several alternatives have been developed. Mainly, those being hybrid and synthetic exosomes.
Alteration of natural exosomes has been labelled under the umbrella term of engineered or designer exosomes. The aim of this process is to display targeting molecules or loading therapeutical compounds within. This type of exosomes can be obtained by two different approaches, through parental cell-based engineering or direct post-isolation engineering, from more to less complex.
In the first case, the cells are genetically modified to produce exosomes with the components of interest in vivo. With this approach, labelling or targeting proteins can be placed in the surface or other components delivered inside. An example could be the production of a protein with an exosome signalling peptide (CD63, CD9, CD81, GPI and Lamp2b), that will lead to the embedding in the exosome membrane. If the molecule is desired to be transported within, other tags can be used to direct the MSMs or Molecule Sorting Module system. This MSMs is the responsible for sorting the proteins and RNA that will be directed to the exosome. For example, ubiquitination tags have been proved to help in this process.
The second approach, direct post-isolation engineering, involves the modification of the exosomes after the isolation has been done. The addition of molecules in the exosomes can be achieved by manipulation methods such as sonication extrusion, incubation, freeze-thaw and bioconjugation. Another strategy for post-isolation modification is the fusion with synthetic liposomes containing the desired components, producing what are called hybrid exosomes.
In the bottom-up strategy we have fully synthetic or artificial exosomes using plain liposomes as a blank canvas and adding the characteristic exosome markers, lipids and contents (proteins and RNA). Also referred to as exosome-mimetics, the synthetic exosomes are less variable and allow the incorporation of targeting ligands and contents in an easier and controlled manner. They are more suitable for pharmaceutical uses since they are highly reproducible and easier to scale up the manufacturing.
- VALIDATION & QUALITY CONTROL
- CANCER TREATMENT
- INMUNOMODULATING RESPONSE
- MOLECULAR THERAPY
- BRAIN DRUG DELIVERY
- OCULAR DRUG DELIVERY
- TISSUE ENGINEERING