ZIF-8 nanocarriers synthesized by co-encapsulating resveratrol and cellulase for biomedical applications

Drug conjugation with enzymes is one of the innovative antibacterial nanocarriers used as a delivery system for cancer therapy. Zeolitic imidazolate framework-8 (ZIF-8) was synthesized, dual encapsulated with cellulase (CL) enzyme, and resveratrol (Resv) drug formed ZIF-8@CL&Resv. Cellulase and resveratrol hydrophobic nature have bound them together and imparted a negative charge on the ZIF-8, resulting in the decrease of zeta potential from 22.7 mV (ZIF-8) to 3.82 mV (ZIF-8@CL&Resv). The cellulase like a scaffold regulated the pH-responsive release of resveratrol enhancing its bioavailability. Molecular docking studies provided evidence of the major interaction between the biofilm-related proteins with cellulase and resveratrol. The encapsulated cellulase showed high enzymatic activity and possibly exhibited antibacterial effects by dissolving the biofilm and exposing bacteria to resveratrol action. Resveratrol released sustainably exhibited significant antioxidant and antibacterial activity against selected bacterial species. ZIF-8@CL&Resv exhibited high biocompatibility and had a potent cytotoxic effect against triple-negative breast cancer cells MDA MB 231 with an IC₅₀-value of 17.18 μg/mL compared to ZIF-8 control with 90.47 μg/mL. ZIF-8@CL&Resv treatment led to 61.81 % cell death, apoptosis induction, increased ROS generation, and decreased mitochondrial membrane potential. Overall, data demonstrated that ZIF-8@CL&Resv is a novel drug release system and a potential catalytic nanoparticle for antimicrobial and anticancer applications.