Reactive oxygen species-sensitive nanophotosensitizers of aminophenyl boronic acid pinacol ester conjugated chitosan-g-methoxy poly(ethylene glycol) copolymer for photodynamic treatment of cancer

Abstract

The aim of this study is to prepare reactive oxygen species (ROS)-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) and photodynamic tumor therapy. For this purpose, thiodipropionic acid (TDPA) was conjugated with phenyl boronic acid pinacol ester (PBAP) (TDPA-PBAP conjugates) and then the TDPA-PBAP conjugates were attached to the chitosan backbone of chitosan-g-methoxy poly(ethylene glycol) (ChitoPEG) copolymer (ChitoPEG-PBAP). Ce6-incorporated ChitoPEG-PBAP nanophotosensitizers have an ROS-sensitive manner in vitro. The size of ChitoPEG-PBAP nanoparticles increased or disintegrated in a responsive manner against H2O2 concentration. The Ce6 release rate from ChitoPEG-PBAP nanophotosensitizers also increased by adding H2O2. These results indicated that nanophotosensitizers have sensitivity against ROS and showed triggered Ce6 release behavior. ChitoPEG-PBAP nanophotosensitizers can be more efficiently internalized into cancer cells compared to Ce6 alone and then produce ROS in a more efficient manner. Furthermore, ChitoPEG-PBAP nanophotosensitizers suppressed the viability of cancer cells in vitro and tumor growth in vivo with higher efficacy compared to Ce6 alone. Furthermore, ChitoPEG-PBAP nanophotosensitizers were efficiently delivered to irradiated tumor tissues, indicating that ChitoPEG-PBAP nanophotosensitizers can be delivered to the tumor with ROS-sensitive manner. We suggest that a ChitoPEG-PBAP nanophotosensitizer is a promising candidate for photodynamic therapy of cancers.

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

“…Furthermore, CAPE-loaded poly(DL-lactide-co-glycolide) nanoparticles are more effective in the reduction of mutagenicity than the free CAPE itself [40]. We also prepared CAPE-incorporated nanoparticles using HAsPBPE conjugates since HA is a biocompatible and water-soluble biopolymer, and TbEA-PBPE moiety acts as a hydrophobic moiety in polymer backbone [45]. Then, HAsPBPE conjugates may form core-shell type nanoparticles, i.e., HA acts as an outershell of the nanoparticles while TbEA-PBPE is composed of the hydrophobic inner-core of the nanoparticles.…”

“…Furthermore, nanoparticles can be modified to be sensitive to physicochemical stimulus such as radiation, pH, ROS, magnetic field, and light [32][33][34][35][36][37]. HAsPBPE nanoparticles can respond to ROS since the PBPE moiety and thiol group in TbEA in the polymer backbone are known to have ROS-sensitivity and these moieties are able to be decomposed in the oxidative stress [45].…”

Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells

“…Then, abnormalities of the tumor microenvironment endow nanoparticles to be sensitive to tumor. Particularly, nanoparticles having ROS-sensitivity gives an opportunity to target tumor tissue to maximize anticancer drug exposure in the site of higher ROS level [ 44 , 45 ]. Jang et al reported that biodegradable nanofiber mats having diselenide linkages have responsiveness against ROS and then specifically release anticancer drug according to ROS level in aqueous solution [ 45 ].…”