Sericin-coated MnO(2)@CeO(2) nanocatalysts enable pH-responsive and synergistic vincristine delivery for lung cancer therapy.

The advancement of multifunctional nanocarriers is crucial for improving cancer treatment. This study explores the synthesis, characterization, molecular modeling, and in vitro evaluation of MnO(2)-based nanocatalysts (MnO(2), MnO(2)@CeO(2), and MnO(2)@CeO(2)-Vin-Ser) designed to enhance anticancer activity through synergistic mechanisms. Physicochemical analyses confirmed the successful incorporation of cerium oxide (CeO(2)), vincristine (Vin), and sericin (Ser) into MnO(2), with sericin playing a vital role in improving nanocarrier stability in aqueous and biological environments. This stability enabled the controlled release of vincristine, ensuring prolonged therapeutic effects.In vitro studies on A549 lung cancer cells demonstrated concentration- and time-dependent cytotoxicity, with MnO(2)@CeO(2)-Vin-Ser exhibiting the highest potency. At 48 h, IC50 values decreased to 100 μg/ml, 50 μg/ml, and 25 μg/ml for MnO(2), MnO(2)@CeO(2), and MnO(2)@CeO(2)-Vin-Ser, respectively. Cellular uptake studies confirmed effective internalization of MnO(2)@CeO(2)-Vin-Ser at pH 6, mediated by charge reversal and sericin-facilitated endocytosis, leading to DNA damage and apoptosis. Apoptosis analysis revealed selective activation of apoptotic pathways with minimal necrosis, reducing inflammatory risks. Reactive oxygen species (ROS) measurements indicated oxidative stress induction by MnO(2)@CeO(2), while sericin mitigated excessive ROS production. These findings highlight MnO(2)@CeO(2)-Vin-Ser as a promising nanoplatform for targeted, effective cancer therapy.