Metal-based biomaterials for cancer gene therapy

Gene therapy holds immense potential to correct genetic aberrations, offering revolutionary prospects for cancer treatment and cures. Compared to conventional therapies, gene therapy demonstrates distinct advantages, including less dosing requirements, reduced toxicity, and the avoidance of drug resistance. However, challenges still exist for the clinical application of gene therapy to cancer treatment, including off-target effect, extended treatment duration, and suboptimal therapeutic efficacy. Gene therapies predominantly rely on a variety of gene regulation tools, such as DNAzymes and RNA interference biomaterials, and gene editing tools like CRISPR-based technologies. Metal ions play crucial and multifaceted roles in enhancing the effectiveness of gene therapy. As enzymatic cofactors, metal ions significantly enhance catalytic activity, and they also serve as functional components in the design of gene delivery vectors, thereby improving therapeutic outcomes. However, the potential of metal-based biomaterials in cancer gene therapy has yet to be comprehensively overviewed. This review provides an in-depth analysis of the roles of metal ions in augmenting gene regulation and gene editing tools, highlighting their contributions to therapeutic efficacy, precision, and the resolution to existing challenges in cancer gene therapy. • A comprehensive review of the latest advances in metal-based biomaterials and their therapeutic implications. • A detailed discussion on the roles of metal ions to regulate biological systems, including enhancing enzymatic activity, structural stability, and gene delivery precision. • A forward-looking evaluation of innovative metal-based biomaterials and their potential for cancer gene therapy.