Methods for loading therapeutics into extracellular vesicles and generating extracellular vesicles mimetic-nanovesicles

Methods. 2020 May 1;177:103-113. doi: 10.1016/j.ymeth.2020.01.001. Epub 2020 Jan 7.

Abstract

Extracellular vesicles (EVs) are membrane bound vesicles released into the extracellular environment by eukaryotic and prokaryotic cells. EVs are enriched in active biomolecules and they can horizontally transfer cargo to recipient cells. In recent years EVs have demonstrated promising clinical applications due to their theragnostic potential. Although EVs have promising therapeutic potential, there are several challenges associated with using EVs before transition from the laboratory to clinical use. Some of these challenges include issues around low yield, isolation and purification methodologies, and efficient engineering (loading) of EVs with therapeutic cargo. Also, to achieve higher therapeutic efficiency, EV architecture and cargo may need to be manipulated prior to clinical application. Some of these issues have been addressed by developing biomimetic EVs. EV mimetic-nanovesicles (M-NVs) are a type of artificial EVs which can be generated from all cell types with comparable characteristics as EVs for an alternative therapeutic modality. In this review, we will discuss current techniques for modifying EVs and methodology used to generate and customize EV mimetic-nanovesicles.

Keywords: Cargo modification; Engineering; Exosome mimetic-nanovesicles; Extracellular vesicles; Therapeutic loading.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Bioengineering / methods*
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / metabolism
  • Calcium Chloride / chemistry
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Drug Compounding / methods*
  • Drug Delivery Systems / methods*
  • Electroporation / methods
  • Extracellular Vesicles / chemistry
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / transplantation
  • Gene Expression
  • Humans
  • Lipids / chemistry
  • Lysosomal-Associated Membrane Protein 2 / genetics
  • Lysosomal-Associated Membrane Protein 2 / metabolism
  • Milk Proteins / genetics
  • Milk Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sepsis / genetics
  • Sepsis / metabolism
  • Sepsis / pathology
  • Sepsis / therapy*
  • Sonication / methods
  • Tetraspanins / genetics
  • Tetraspanins / metabolism

Substances

  • Antigens, Surface
  • LAMP2 protein, human
  • Lipids
  • Lipofectamine
  • Lysosomal-Associated Membrane Protein 2
  • MFGE8 protein, human
  • Milk Proteins
  • Recombinant Fusion Proteins
  • Tetraspanins
  • Calcium Chloride