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Life sciences · Review
Frontiers in Pharmacology · September 17, 2026
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Introduction Porous silicon nanoparticles (pSiNPs) are promising carriers for anticancer therapy because of their high drug-loading capacity, modifiable surface properties, and potential for stimulus-responsive drug release. This systematic review assessed the efficacy and safety of drug-loaded pSiNPs in in vitro and in vivo cancer models. Methods Searches were conducted from database inception to 30 July 2026. Eligible studies were controlled original investigations evaluating pSiNPs loaded with at least one anticancer drug and reporting quantitative antitumor outcomes. Study selection followed PRISMA 2020 guidelines, and the protocol was registered in PROSPERO (CRD420251076592). Given the substantial methodological heterogeneity, findings were synthesized narratively. In vitro study reliability was appraised using an explicitly adapted ToxRTool framework, whereas animal-study risk of bias was assessed with the SYRCLE tool. Results The search strategy identified 974 records, of which 22 met the inclusion; eight included animal experiments. Targeting ligands, polymeric coatings, and pH-, redox-, magnetic-, or near-infrared-responsive systems generally improved cellular uptake, drug release, cytotoxicity, and antitumor activity relative to study-specific comparators. Most in vitro studies were classified as reliable with restrictions, while several animal-study domains had unclear risk of bias because key safeguards were insufficiently reported. Conclusion Drug-loaded pSiNPs show promising preclinical anticancer activity, but the evidence is dominated by in vitro proof-of-concept studies. Animal evidence remains limited and does not establish long-term systemic safety or biocompatibility. Standardized nanoparticle characterization, rigorous animal designs, and comprehensive long-term safety and biodistribution studies are required before clinical translation. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251076592.