Advances in stimuli-responsive nanoparticles for cancer therapy: Mechanisms, functional materials, and emerging technologies

Cancer is a multifactorial disease and hence demands different therapeutic strategies to arrest its progression and recurrence. Conventional therapies such as chemotherapy and radiotherapy, while widely used, present limitations, including low specificity, systemic toxicity, and drug resistance. In this context, nanotechnology has emerged as a promising non-invasive approach, offering enhanced targeting, controlled drug release, and reduced side effects. This critical review integrates the latest advancements in stimuli-responsive smart nanoparticles, including polymeric, lipid-based, and inorganic nanocarriers, while emphasizing both their mechanistic aspects and translational challenges. Special emphasis is given to exogenous and endogenous stimuli-responsive nanoparticles, such as pH, redox, enzyme, and magnetic field-responsive nanomaterials, which enable site-specific drug activation and minimize off-target effects. Furthermore, we discuss cutting-edge technologies, including CRISPR-Cas9-loaded nanoparticles for gene silencing, AI-driven nanoparticle modeling for precision medicine, biomimetic nanoparticles for enhanced biocompatibility, and liquid biopsy-integrated nanodiagnostics for early cancer detection. The diversity of nanomaterials and their action in different classes is evaluated to improve cancer treatment by using a range of therapeutic agents. Despite their potential, our analysis highlights several challenges for the clinical application of nanoparticle-based delivery systems, including stability, toxicity, long-term safety, and regulatory aspects. This comprehensive and integrative approach provides new insights to guide future research and clinical translation of smart nanomedicine in oncology.