Supramolecular Caffeic Acid and Bortezomib Nanomedicine: Prodrug Inducing Reactive Oxygen Species and Inhibiting Cancer Cell Survival

Ludwig Erik Aguilar; Se Rim Jang; Chan Hee Park; Kang Min Lee

doi:10.3390/pharmaceutics12111082

Supramolecular Caffeic Acid and Bortezomib Nanomedicine: Prodrug Inducing Reactive Oxygen Species and Inhibiting Cancer Cell Survival

Pharmaceutics. 2020 Nov 11;12(11):1082. doi: 10.3390/pharmaceutics12111082.

Authors

Ludwig Erik Aguilar¹, Se Rim Jang^{1

2}, Chan Hee Park^{1

2

3}, Kang Min Lee⁴

Affiliations

¹ Department of Bionanosystem Engineering, Jeonbuk National University, Jeollabuk-do 54896, Korea.
² Department of Bionanotechnology and Bioconvergence Engineering, Graduate School, Jeonbuk National University, Jeollabuk-do 54896, Korea.
³ Division of Mechanical Design Engineering, Jeonbuk National University, Jeollabuk-do 54896, Korea.
⁴ Department of Molecular Biology, College of Natural Science, Jeonbuk National University, Jeollabuk-do 54896, Korea.

Abstract

Phenolics from plant materials have garnered attention in nanomedicine research, due to their various medicinal properties. Caffeic acid, a phenolic compound that is abundant in coffee beans, has been proven to have anticancer effects, due to its reactive oxygen species (ROS)-inducing properties. Here, a supramolecular nanomedicine was designed using caffeic acid molecule and the synthetic anticancer drug bortezomib, via catechol-boronic acid conjugation and Fe(III) ion crosslinking. Bortezomib is a proteasome-inhibiting drug and its boronic acid functional group can bind to caffeic acid's catechol moiety. By having a nanoparticle formulation that can deliver bortezomib via intracellular endocytosis, the catechol-boronic acid conjugation can be dissociated, which liberates the boronic acid functional group to bind to the 26S proteasome of the cell. The ROS-inducing property of caffeic acid also complements the bortezomib payload, as the latter suppresses the survival mechanism of the cell through NF-κB inhibition.

Keywords: bortezomib; caffeic acid; cancer treatment; phenolics; prodrug nanomedicine.