ECM-Mimetic CoMn-LDH Integrated PCL/PAAm Nanofibrous Hydrogel for Effective Multifunctional Drug Delivery and Fenton-Like Chemodynamic Cancer Therapy

Conventional localized drug delivery systems (DDS) and chemodynamic therapy (CDT) platforms often lack structural integrity, hydration-mediated transport control, and architectures capable of sustaining redox activity at tumor sites. Here, we report a hybrid nanofibrous hydrogel that integrates CoMn layered double hydroxide (CoMn-LDH) within electrospun polycaprolactone (PCL) fibers, followed by a polyacrylamide (PAAm) hydrogel coating to construct a localized, ECM-mimetic therapeutic platform with dual functionality. Unlike Conventional CDT systems that treat drug delivery and catalytic activity independently, this design integrates a hydrated diffusion network with redox-active centers within a single architecture. The CoMn@PCL/PAAm HNF exhibits enhanced wettability of 26.4° and pronounced swelling-assisted transport, enabling sustained and non-Fickian release with cumulative release of 96.99%, 86.77%, and 97.83% at pH 6.2, 7.4, and 8.8, respectively. Furthermore, the system promotes peroxide-activated ROS generation, enhances intracellular oxidative stress, and induces apoptosis-mediated cytotoxicity against HuH7 and SiHa cells, with inhibition rates of 64.73% and 52.03%, respectively, while remaining nonhemolytic. These results indicate that interface-engineered transport reaction coupling governs both drug diffusion and ROS generation, highlighting the potential of CoMn@PCL/PAAm HNF for CDT integrated implantable anticancer applications with reduced system toxicity.