Engineering nanoplex platforms for enhanced transfection and gene expression in cancer therapy

Abstract

Cancer remains a leading cause of morbidity and mortality worldwide, accounting for millions of new cases and deaths annually. Despite advances in conventional chemotherapy, treatment outcomes are often limited by poor selectivity, systemic toxicity, drug resistance and suboptimal pharmacokinetics. Nucleic acid-based therapies are promising strategies for targeted cancer treatment; however, their clinical application is hindered by rapid degradation, poor cellular uptake and low transfection efficiency. Nanotechnology-based delivery systems have therefore been explored to overcome these barriers. Among these, nanoplexes are a versatile platform for gene delivery due to their ability to complex, protect and transport nucleic acids into target cells. This review focuses on the engineering of nanoplex platforms for enhanced transfection and gene expression in cancer therapy. We provide a comprehensive analysis of the current progress in nanoplex design and application and discuss advances in nanoplex-mediated gene delivery across cancer types, highlighting their transfection efficiency, gene expression, gene knockdown and safety profiles. Brief comparisons with other non-viral delivery systems are included to contextualize their relative advantages and limitations. Finally, the review outlines key challenges and future opportunities for the clinical translation of nanoplex-based gene therapies.