Amphiphilic TEMPO-Functionalized Block Copolymers: Synthesis, Self-Assembly and Redox-Responsive Disassembly Behavior, and Potential Application in Triggered Drug Delivery

A novel range of amphiphilic redox-responsive 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-functionalized diblock copolymers poly(ethylene glycol)-b-poly(2,2,6,6-tetramethylpiperidine-1-oxyl-4-yl methacrylate-co-N-isopropylacrylamide [PEG-b-P(TMA-co-NIPAM)] have been synthesized in this work via reversible addition–fragmentation chain transfer (RAFT) polymerization followed with functionality transformation. With the possession of the hydrophilic PEG block and the hydrophobic TEMPO-containing block, these amphiphilic diblock polymers can conveniently self-assemble to form stable uniformly sized radical-containing nanoparticles (RNPs), which can thus act as nanovessels to carry drugs. More interestingly, the self-assembled RNPs exhibit the unique reduction-responsive disassembly upon addition of vitamin C (VC) as a representative reducing agent due to the drastic drop in the surface hydrophobicity following reduction of the TEMPO units. In the proof-of-concept experiments, the VC-triggered release of the encapsulated R6G dye as the model payload from the RNPs at controllable rates has been successfully demonstrated. Meanwhile, the cytotoxicity study with CCK-8 assay confirms the TEMPO-containing block copolymers and their reduced ones are nontoxic at a concentration up to 500 μg mL–1. This series of amphiphilic diblock copolymers is thus highly promising for potential application in triggered drug delivery.