An Overview of Exosomes in Cancer Therapy: A Small Solution to a Big Problem

Abstract

Exosomes are defined as a type of extracellular vesicle released when multivesicular bodies of the endocytic pathway fuse with the plasma membrane. They are characterized by their role in extracellular communication, partly due to their composition, and present the ability to recognize and interact with cells from the immune system, enabling an immune response. Their targeting capability and nanosized dimensions make them great candidates for cancer therapy. As chemotherapy is associated with cytotoxicity and multiple drug resistance, the use of exosomes targeting capabilities, able to deliver anticancer drugs specifically to cancer cells, is a great approach to overcome these disadvantages. The objective is to assess treatment efficiency in reducing tumor cells, as well as overall safety and response by cancer carriers. So far, results show exosomes as a promising therapeutic strategy in the fight against cancer. This review summarizes the characteristics and composition of exosomes, as well as explaining in detail the involved parties in the origin of exosomes. Furthermore, some considerations about exosome application in immunotherapy are addressed. The main isolation and loading methods are described to give an insight into how exosomes can be obtained and manipulated. Finally, some therapeutic applications of exosomes in cancer therapy are described.

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

“…From these modified cells, exosomes that already contain the incorporated desired drug are then secreted and isolated [7,15,16,77]. This is a relatively simple method, but it is not possible to provide control over loading efficiency [78]. This method was performed on mesenchymal stromal cells into which melatonin was incorporated.…”

“…Another method is chemical transfection, in which exosomes and cargo are incubated with the surfactant, causing the formation of pores in the membrane and thus the penetration of drugs. The most frequently used surfactant is saponin, and thus this method is also called saponin-assisted loading [14,78]. Warren et al [81] established that encapsulation of siRNA into bovine milk-derived exosomes by chemical transfection was significantly more efficient than by electroporation.…”

“…From these modified cells, exosomes that already contain the incorporated desired drug are then secreted and isolated [7,15,16,77]. This is a relatively simple method, but it is not possible to provide control over loading efficiency [78]. This method was performed on mesenchymal stromal cells Principle of pre-isolation exosomes modification methods (co-incubation and gene editing (intended for the incorporation of RNA and proteins), where the modification of exosomes is performed before isolating exosomes from parental cells (summarized from [7,11,76]).…”

“…The only exception is co-incubation in internal modifications as well as hybridization and direct incorporation in surface modifications [14,16,85,89,94-96]. The main advantages (green) and disadvantages (red) of exosome preparation methods for interior (pre-isolation and post-isolation modification methods) and surface modifications (genetic engineering of parental cells and direct modification of isolated exosomes; summarized from [7,11,14,16,78,85,89,90,[94][95][96]).…”

Exosomes: Next generation medicine

“…The main components of exosomes are DNA, nucleic acids, lipids and proteins. Proteins usually found in exosomes include that connected with membrane transport, for example, annexins, RAB GTPases, flotillins, MVB-producing proteins like ALIX, and tumor susceptibility gene 101 proteins (TSG101) [7]. Exosomes are packaged with a conserved set of protein, for example, tetraspanins, including CD9, CD63, and CD81 as well as heat shock proteins (HSP70).…”