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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\u2010related microenvironment signals or externally applied energy into site\u2010specific therapeutic activation. This review discusses stimuli\u2010responsive 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\u2010responsive systems, including pH\u2010, enzyme\u2010, redox\u2010, reactive oxygen species (ROS)\u2010, hypoxia\u2010, glucose\u2010, ATP\u2010, ionic\u2010strength\u2010, and urea\u2010responsive MSNs, and extrinsic systems triggered by light, magnetic fields, ultrasound, temperature, and electric fields. Multi\u2010stimuli\u2010responsive and combination systems are discussed as examples of how tumor cues, external activation, imaging, and therapy can be coordinated. The final section considers disease\u2010oriented design, cancer immunotherapy, degradable silica frameworks, long\u2010term safety, reproducible manufacturing, and clinical translation. Together, these topics show how MSNs can move from porous drug reservoirs toward functional nanoplatforms for precision oncology.<\/jats:p>","DOI":"10.1002\/smo2.70103","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:15:43Z","timestamp":1790316943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Smart mesoporous silica nanoparticles for precision cancer therapy: Tumor targeting and stimuli\u2010responsive controlled release"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2899-2123","authenticated-orcid":false,"given":"Majdi","family":"Al\u2010Amili","sequence":"first","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"},{"name":"Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Qujing College of Medicine &amp; Health Sciences  Qujing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6619-7705","authenticated-orcid":false,"given":"Zhu","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.12.007"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113991"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nwnano.2026.100203"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17020245"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-025-02102-z"},{"key":"e_1_2_11_7_1","first-page":"101","volume":"10","author":"Joo J. 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