Magneto-Fluorescent Mn-Doped CD@ZIF-8@Kappa Carrageenan Biohydrogel—A Dual Model Therapeutic and Diagnostic Agent for Targeted Drug Delivery and Cancer Therapy

Abstract

Manganese-based nanomaterials have emerged as highly promising candidates for cancer theranostic owing to their unique multifunctional capabilities in chemodynamic therapy, immune regulation, and magnetic resonance imaging (MRI). Herein, we present a biodegradable and multifunctional nanotherapeutic platform constructed by encapsulating manganese-doped carbon dots (MnCDs) within the zinc-based metal−organic framework (MOF)-ZIF-8 and further embedding the composite into a K-Carrageenan (K-Car) biopolymeric hydrogel matrix, referred to as the MnCD@ZIF-8@K-Car gel. This nanoplatform was designed for the efficient encapsulation of the anticancer drug 5-fluorouracil (5 FU) and exhibited a pronounced pH-responsive drug release profile under tumor-mimicking acidic conditions. The MnCD@ZIF-8@K-Car system demonstrated intense blue fluorescence, enabling effective in vitro fluorescence imaging, and exhibited excellent T1−T2-weighted MRI contrast enhancement at low concentrations. Moreover, the nanocomposite catalyzed Fenton-like reactions with endogenous hydrogen peroxide in the microenvironment, producing highly reactive hydroxyl radicals that induce oxidative damage to intracellular biomolecules and suppress tumor cell proliferation. In addition, the ZIF-8 imparted notable bacteriostatic activity against Gram-negative Escherichia coli. Cellular internalization and cytotoxicity investigations revealed selective toxicity toward folate-receptor-overexpressing HeLa cells, while comparatively reduced cytotoxic effects were observed in MDA-MB-231 breast cancer cells and nonmalignant L929 fibroblasts. Overall, this multifunctional MnCD@ZIF-8@K-Car nanohydrogel integrates pH-responsive chemotherapy, chemodynamic therapy, biosensing, dual-modal imaging, and antibacterial functionality within a single system, highlighting its strong potential for advanced cancer theranostic applications.