Design of Reduction-Responsive Copolymer-Based Nanoparticles for Enhanced Anticancer Drug Delivery

Polymer-based nanoparticles with tumor-targeting ability, controlled-release properties and good biocompatibility are of great interest for anticancer drug delivery. Herein, two amphiphilic reduction-responsive copolymers self-assembled nanoparticles (mPEG-Cys-PCL and mPEG-Ami-PCL) along with their inert counterpart (mPEG-Hex-PCL) were prepared and evaluated. These three copolymers were synthesized by conjugating mPEG and PCL with different linkers and characterized by proton nuclear magnetic resonance spectrometry, flourier transform infrared spectrometry and gel permeation chromatography. Nile red (NR) was loaded into the prepared nanoparticles as a model drug to study the in vitro drug release, cellular uptake amount and biodistribution. Dimethylcurcumin (DMC) was loaded into the prepared nanoparticles to study the in vitro antitumor effect. The results show that NR@mPEG-Cys-PCL and NR@mPEG-Ami-PCL nanoparticles exhibit glutathione (GSH)-triggered drug release and NR@mPEG-Ami-PCL nanoparticles display enhanced GSH-responsiveness as compared to NR@mPEG-Cys-PCL. Moreover, NR@mPEG-Ami-PCL nanoparticles possess enhanced cellular uptake amount as compared to NR@mPEG-Hex-PCL and NR@mPEG-Cys-PCL nanoparticles. DMC@mPEG-Ami-PCL nanoparticles possess the highest in vitro antitumor effect. In biodistribution study, both NR@mPEG-Cys-PCL and NR@mPEG-Ami-PCL nanoparticles show reduced organ distribution and similar tumor accumulation as compared to NR@mPEG-Hex-PCL nanoparticles. The mPEG-Ami-PCL nanoparticles developed in this work show great potential for anticancer drug delivery.