Caffeic Acid Phenethyl Ester-Incorporated Radio-Sensitive Nanoparticles of Phenylboronic Acid Pinacol Ester-Conjugated Hyaluronic Acid for Application in Radioprotection.

Jae-Heun Lee,Young-Il Jeong,Sohi Kang,Dong-Yeon Lee,Min-Kyung Lee,Hye-Lim Lee,Seon-Hee Choi,Sang-Heon Lee,Hyo-Young Lee

doi:10.3390/ijms22126347

Abstract

We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.

Highlights

Ionizing radiation has been extensively used for therapeutic and diagnostic purposes of human disease [1,2,3,4,5]
We showed that caffeic acid phenetyl ester (CAPE)-incorporated nanoparticles as well as CAPE effectively suppressed intracellular reactive oxygen species (ROS) accumulation induced by the irradiation of cells
CAPE-incorporated nanoparticles showed extended survivability of mice after irradiation at 7 Gy compared to CAPE itself (Figure 7). These results indicated that CAPE-incorporated nanoparticles have a superior activity against radiation-induced injury

Summary

Introduction

Ionizing radiation has been extensively used for therapeutic and diagnostic purposes of human disease [1,2,3,4,5]. Even though ionizing radiation is widely utilized for diagnosis/therapy of human diseases, repeated or high dose radiation is closely associated with undesirable effects against healthy cells and tissues since ionizing radiation induces oxidative stress in the surrounding field of irradiation [6,7,8]. Irradiation causes DNA damage and metabolic stress in healthy cells and tissues since it elevates the ROS level in disease cells/tissues and in healthy cells/tissues [7,8]. Epigallocatechin gallate (EGCG) is known to decrease ROS levels, suppress radiation-induced intestinal injury, and prolong the survival time of mice [10]

Methods

Results

Conclusion