Exosomes as Emerging Drug Delivery and Diagnostic Modality for Breast Cancer: Recent Advances in Isolation and Application

Abstract

Breast cancer (BC) is the most common type of malignancy which covers almost one-fourth of all the cancers diagnosed in women. Conventionally, chemo-, hormonal-, immune-, surgery, and radiotherapy are the clinically available therapies for BC. However, toxicity and other related adverse effects are still the major challenges. A variety of nano platforms have been reported to overcome these limitations, among them, exosomes provide a versatile platform not only for the diagnosis but also as a delivery vehicle for drugs. Exosomes are biological nanovesicles made up of a lipidic bilayer and known for cell-to-cell communication. Exosomes have been reported to be present in almost all bodily fluids, viz., blood, milk, urine, saliva, pancreatic juice, bile, peritoneal, and cerebrospinal fluid. Such characteristics of exosomes have attracted immense interest in cancer diagnosis and therapy. They can deliver bioactive moieties such as protein, lipids, hydrophilic as well as hydrophobic drugs, various RNAs to both distant and nearby recipient cells as well as have specific biological markers. By considering the growing interest of the scientific community in this field, we comprehensively compiled the information about the biogenesis of exosomes, various isolation methods, the drug loading techniques, and their diverse applications in breast cancer diagnosis and therapy along with ongoing clinical trials which will assist future scientific endeavors in a more organized direction.

Keywords: biomarker; breast cancer; chemotherapy; diagnosis; drug delivery; exosomes; targeted therapy.

Figure 1

The composition of the typical exosome. Exosomes are nano-sized extracellular vesicles composed of a phospholipid bilayer, proteins such as TSG 101, Integrins, Alix, HSP, nucleic acids such as miRNA, mRNA, DNA, and many other receptors.

Figure 2

Different sources, viz., urine, saliva, cancer cells, platelets, milk, cerebrospinal fluid, mesenchymal stem cells, and red blood cells majorly reported for the isolation of exosomes and their use in diagnosis and drug delivery.

Figure 3

The mechanism of exosome biogenesis. The biogenesis of exosomes is initiated with endocytosis which includes cell membrane inward budding and enclosing of biologically active cargos, which further leads to the development of the endosome. The enclosed cargos are then categorized into smaller vesicles which bud from the perimeter membrane into endosome lumen forming multivesicular bodies (MVBs). Further, MVBs either merge with the lysosome for degeneration or with the inner plasma membrane through RAB or soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) to release exosomes.

Figure 4

Common steps followed during the separation of exosomes via ultrafiltration. Here, the samples are passed through multiple membranes of different pore sizes such as 0.8, 0.45, 0.22 µ which result in the concentration of the sample after every pass through the filters of different pore sizes.

Figure 5

Schematic diagram showing different methods of loading cargos into exosomes through pre-loading and post-loading strategies: (A) incubation with parent cell; (B) incubation; (C) sonication; (D) electroporation; (E) detergent method; (F) excursion; (G) freeze–thaw cycle.

Figure 6

Schematic diagram showing the application of exosomes as a nanocarrier for targeted drug delivery in cancer.