Stimuli-Responsive Mesoporous Silica Nanoparticles for Precision Cancer Therapy: Design Principles, Cellular Uptake, and Translational Perspectives

Premature drug release in the systemic circulation or at off-target sites remains a major challenge in conventional drug delivery systems, often resulting in reduced therapeutic efficacy and increased systemic toxicity. Nanotechnology-based delivery platforms have emerged as promising strategies to address these limitations. Among them, mesoporous silica nanoparticles (MSNs) have attracted considerable attention due to their high surface area, tunable pore size, large loading capacity, and considerable structural stability. These features enable efficient encapsulation and controlled delivery of therapeutic cargos. Recent advances in MSN engineering have focused on the development of stimuli-responsive systems capable of releasing drugs in response to specific internal or external triggers, such as pH variations, temperature, light, enzymatic activity, and redox conditions (e.g., glutathione). Such smart nanocarriers facilitate site-specific drug release while minimizing off-target effects. This review highlights recent progress in the design and application of stimuli-responsive MSNs for cancer therapy. Particular emphasis is placed on mechanisms of intracellular uptake, factors influencing cellular internalization, and strategies for controlled drug release. In addition, current insights into the biocompatibility and toxicity of MSNs are discussed to provide a comprehensive perspective on their translational potential in cancer nanomedicine.