Oxidation-responsive phenylboronate-bridged block copolymer for targeted cancer drug delivery

Abstract

Nanomedicine has revolutionized cancer therapy by improving targeted drug delivery while mitigating systemic side effects. An effective delivery system must maintain stability in physiological environments while enabling precise and rapid drug release in tumors. The primary challenge lies in designing nanocarriers that are responsive to tumor-specific stimuli. Here, we introduce a novel amphiphilic block copolymer, PEG-Blink-PCL, featuring a phenylboronic ester linker that selectively degrades, responding to reactive oxygen species (ROS), allowing for controlled, site-specific drug release. Our study demonstrates that DOX-loaded PEG-Blink-PCL micelles (B/DOX-M) exhibit excellent stability in the bloodstream yet quickly shed their PEG corona upon exposure to elevated ROS levels, leading to micelle disassembly and efficient DOX release in tumors. This ROS-triggered “shell-removal” strategy significantly augments tumor inhibition while minimizing systemic toxicity in the MDA-MB-231 tumor model. Overall, this study highlights the potential of ROS-responsive PEG-Blink-PCL as a promising platform for effective and precise cancer drug delivery.