Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

Abstract

Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy. Graphical Abstract

Patient-Derived Exosomes as siRNA Carriers in Ovarian Cancer Treatment

“…First, exosomes were collected using differential ultracentrifugation, which is a complicated method which cannot remove the debris inevitably produced during the collection process. Thus, for applications in clinical settings, easier methods of collecting high-quality exosomes are warranted, such as size exclusion chromatography, dense gradient centrifugation, and immunoaffinity capture [14]. Second, although the omentum was used as the exosome source, a laparotomy must be performed to utilize the omentum.…”

“…In addition, if patient-derived exosomes can be used as transport carriers, immune reactions during administration may be avoided. Various preclinical studies have revealed the potential of exosomes as carriers for nucleic acid compounds (such as siRNA and shRNA), proteins (such as 20S proteasome and catalase), and drugs (such as dopamine, paclitaxel, and doxorubicin) [11,14,15]. Furthermore, we recently demonstrated the efficacy of exosomes as microRNA carriers [16,17].…”

Exosomes in Vascular/Neurological Disorders and the Road Ahead

“…It is possible to engineer tissue-type-specific or cell-type-specific targeting ligands onto their surface [83], and exosomes can be loaded with various cargos, including nucleic acids, proteins, and low-molecular-weight therapeutic agents [12]. Furthermore, the potential for personalized medication is offered through the readministration of isolated exosomes loaded with therapeutic agents into the patient [84,85]. However, numerous challenges must be addressed to render exosomes applicable for therapeutic purposes in the treatment of central nervous system diseases.…”

Molecular Determinants Involved in the Docking and Uptake of Tumor-Derived Extracellular Vesicles: Implications in Cancer

“…Additionally, a better understanding of the molecules dictating the docking and uptake of EVs can help improve the effectiveness of emerging exosome-based delivery strategies and technologies for cancer therapy developed by biotech companies, either as platforms to load and deliver therapeutic miRNAs and/or proteins or as immunomodulating agents [ 157 , 158 , 159 , 160 , 161 , 162 , 163 ].…”