Smart mesoporous silica nanoparticles for precision cancer therapy: Tumor targeting and stimuli-responsive controlled release.

Mesoporous silica nanoparticles (MSNs) are useful carriers for precision cancer therapy because their ordered pores, large surface area, controllable particle morphology/structure, and modifiable surface support high cargo loading, tumor targeting, and controlled release. Their role is no longer limited to passive drug storage. By adding molecular gatekeepers, cleavable linkers, responsive polymers, ligands, magnetic components, photosensitizers, or imaging modules, MSNs can translate tumor-related microenvironment signals or externally applied energy into site-specific therapeutic activation. This review discusses stimuli-responsive MSNs from the viewpoint of molecular design and release control. We first examine how shape, size, pore architecture, and surface functionalization influence transport, cellular uptake, loading, and release. We then summarize passive and active targeting strategies, followed by intrinsic stimuli-responsive systems, including pH-, enzyme-, redox-, reactive oxygen species (ROS)-, hypoxia-, glucose-, ATP-, ionic-strength-, and urea-responsive MSNs, and extrinsic systems triggered by light, magnetic fields, ultrasound, temperature, and electric fields. Multi-stimuli-responsive and combination systems are discussed as examples of how tumor cues, external activation, imaging, and therapy can be coordinated. The final section considers disease-oriented design, cancer immunotherapy, degradable silica frameworks, long-term safety, reproducible manufacturing, and clinical translation. Together, these topics show how MSNs can move from porous drug reservoirs toward functional nanoplatforms for precision oncology.