Biotechnology and Bioprocess Engineering 2021; 26(1): 78-85  
Phenylboronic Acid-conjugated Exosomes for Enhanced Anticancer Therapeutic Effect by Increasing Doxorubicin Loading Efficiency
Haneul Kim, Su Jin Kang, and Won Jong Rhee
Haneul Kim†, Su Jin Kang†, Won Jong Rhee
Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Korea
Won Jong Rhee*
Division of Bioengineering, Incheon National University, Incheon 22012, Korea
Tel: +82-32-835-8299; Fax: +82-32-835-0763
E-mail: wjrhee@inu.ac.kr
†Equal contribution.
Received: April 8, 2020; Revised: July 8, 2020; Accepted: July 26, 2020; Published online: February 28, 2021.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Anticancer drugs, including doxorubicin (DOX), have been widely used for cancer treatment, but these chemotherapeutic drugs have some issues to address because of their associated side effects, such as cytotoxicity. Various synthetic delivery vehicles for anticancer drugs have been developed to encapsulate and transfer them to cancer cells. However, these delivery vehicles also have high cytotoxicity and immunogenicity. Recently, exosomes have been highlighted as candidates for anticancer drug delivery vehicles with fewer side effects. Exosomes are nanosized particles that are produced from cells, and high concentrations of exosomes are already present in the human body. To develop exosome-based anticancer therapeutics, high drug concentrations should be loaded into exosomes. In this context, phenylboronic acid (PBA) was introduced and chemically conjugated to the exosome surface to load DOX to exosomes. Consequently, a high amount of DOX was efficiently loaded onto the PBA-conjugated exosomes. The DOX-loaded PBA-conjugated exosomes were applied to MDA-MB-231 breast cancer cells and showed enhanced cancer cell cytotoxicity compared to free DOX and DOXloaded non-conjugated exosomes. Therefore, using PBAconjugated exosomes for delivering DOX to cancer cells can be a promising strategy for effectively killing cancer cells because a high amount of DOX can be loaded and delivered.
Keywords: doxorubicin, anticancer drug, delivery vehicles, exosome, phenylboronic acid

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