Abstract
Metastatic bladder cancer (mBC) continues to resist current treatment approaches, largely because aberrant microRNAs (miRNAs) simultaneously fuel epithelial-mesenchymal transition, enable immune system evasion, and promote resistance to therapies. Mounting evidence pinpoints miR-21 as a key oncomiR that amplifies PI3K/AKT signaling, while miR-200c plays a counterbalancing role by maintaining epithelial traits and promoting apoptosis. This makes the combined strategy of suppressing miR-21 while restoring miR-200c an especially compelling, though technically intricate, therapeutic target. Recently, two-dimensional transition-metal carbides and nitrides-known as MXenes-have emerged as promising tools, thanks to their exceptionally high surface area, excellent conductivity, and customizable surface chemistry, all of which make them ideal for shielding miRNAs, delivering them selectively to tumors, and enabling real-time photothermal monitoring. In this review, we weave together insights from epidemiology, molecular oncology, and nanotechnology to chart a translational pathway for applying MXene-based theranostic systems in mBC. We compile mechanistic data regarding miR-21 and miR-200c, detail the MXene physicochemical traits crucial for RNA loading and biosensing, and critically assess polymer-, ligand-, and ion-intercalation methods that improve biocompatibility without compromising electrical performance. Notably, preclinical studies show that MXene scaffolds can co-deliver anti-miR-21 and miR-200c mimics, destroy tumors via near-infrared photothermal therapy, and allow for electrochemical tracking of miRNA activity inside tumors-together achieving a potent, combined blockade of metastatic processes. Persistent challenges, including oxidative degradation, dose-dependent toxicity, and large-scale manufacturing, are addressed alongside promising innovations such as biodegradable surface coatings and machine-learning-assisted material design. Altogether, dual-miRNA theranostics using MXenes hold immense promise as transformative tools for precision treatment of metastatic bladder cancer.