ROS-Responsive PCL–PTK–PCL Nanocarriers for Controlled Release of Nerve Growth Factor and Cytocompatibility Evaluation

Background: Reactive oxygen species (ROS)–induced oxidative stress contributes to neuronal injury during ischemic conditions, creating a need for delivery systems that can release therapeutic molecules in response to oxidative cues. Incorporating thioketal linkages into polymeric materials provides a feasible strategy to construct ROS-degradable carriers. Methods: In this study, a triblock copolymer poly(ε-caprolactone)–thioketal–poly(ε-caprolactone) (PCL–PTK–PCL) was synthesized via ring-opening polymerization using thioketal diol as the initiator. The polymer self-assembled into nanocarriers capable of encapsulating nerve growth factor (NGF). The structural characteristics were analyzed by FTIR and TEM, while the degradation and release behaviors were evaluated under various H₂O₂ concentrations. Cytocompatibility and neuronal viability were assessed using PC12 cells. Results: The PCL–PTK–PCL nanocarriers exhibited uniform spherical morphology with an average size of ~100 nm. The presence of thioketal bonds conferred clear ROS sensitivity, as evidenced by H₂O₂-triggered swelling and accelerated NGF release. The carriers remained stable under non-oxidative conditions and showed good cytocompatibility, maintaining high neuronal cell viability after incubation. Conclusion: The synthesized PCL–PTK–PCL nanocarriers achieved ROS-triggered degradation and controlled NGF release while exhibiting minimal cytotoxicity. These findings confirm their suitability as a basic oxidation-responsive platform for further exploration in oxidative stress–related neuronal studies.