A Review on the Recent Advancements of Polymer-Modified Mesoporous Silica Nanoparticles for Drug Delivery Under Stimuli-Trigger.

Mesoporous silica nanoparticles (MSNs) are gaining popularity in nanomedicine due to their large surface area, variable pore size, great biocompatibility, and chemical adaptability. In recent years, the combination of smart polymeric materials with MSNs has transformed the area of regulated drug administration, particularly under stimuli-responsive settings. Polymer-modified MSNs provide increased stability, longer circulation times, and, most crucially, the capacity to respond to diverse internal (pH, redox potential, enzymes, and temperature) and external (light, magnetic field, and ultrasonic) stimuli. These systems allow for the site-specific, on-demand release of therapeutic molecules, increasing treatment effectiveness while decreasing off-target effects. This review presents a comprehensive analysis of recent advancements in the development and application of polymer-functionalized MSNs for stimuli-triggered drug delivery. Key polymeric modifications, including thermoresponsive, pH-sensitive, redox-responsive, and enzyme-degradable systems, are discussed in terms of their design strategies and therapeutic outcomes. The synergistic use of dual or multiple stimuli-responsive polymers is also highlighted as a promising avenue to enhance precision and control in complex biological environments. Moreover, the integration of targeting ligands and stealth polymers such as PEG further enables selective tumor targeting and immune evasion, broadening the potential clinical applications of these nanocarriers. Recent progress in stimuli-triggered MSNs for combination therapies such as chemo-photothermal and chemo-photodynamic therapy is also covered, emphasizing how polymer modifications enhance responsiveness and therapeutic synergy. Finally, the review discusses current challenges, including scalability, biosafety, and regulatory considerations, and provides perspectives on future directions to bridge the gap between laboratory research and clinical translation.