Emerging Multifunctional Biomaterials for Addressing Drug Resistance in Cancer.

Abstract

Drug resistance remains a major barrier to effective cancer treatment, contributing to poor patient outcomes. Multifunctional biomaterials integrating electrical and catalytic properties offer a transformative strategy to target diverse resistance mechanisms. This review explores their ability to modulate cellular processes, remodel the tumor microenvironment (TME), and enhance drug delivery. Electrically active biomaterials enhance drug uptake and apoptotic sensitivity by altering membrane potentials, ion channels, and intracellular signaling, synergizing with chemotherapy. Catalytic biomaterials generate reactive oxygen species (ROS), activate prodrugs, reprogram hypoxic and acidic TME, and degrade the extracellular matrix (ECM) to improve drug penetration. Hybrid nanomaterials (e.g., conductive hydrogels, electrocatalytic nanoparticles), synergize electrical and catalytic properties for localized, stimuli-responsive therapy and targeted drug release, minimizing systemic toxicity. Despite challenges in biocompatibility and scalability, future integration with immunotherapy, personalized medicine, and intelligent self-adaptive systems capable of real-time tumor response promises to accelerate clinical translation. The development of these adaptive biomaterials, alongside advancements in nanotechnology and AI-driven platforms, represents the next frontier in precision oncology. This review highlights the potential of multifunctional biomaterials to revolutionize cancer therapy by addressing multidrug resistance at cellular, genetic, and microenvironmental levels, offering a roadmap to improve therapeutic outcomes and reshape oncology practice.