In this study, we introduced a multifunctional hollow mesoporous silica-based nanocarrier (HMSN) for the targeted delivery of irinotecan (IRT) to colorectal cancer cells. Due to their large reservoirs, hollow mesoporous silica nanoparticles are suitable platforms for loading significant amounts of drugs for sustained drug release. To respond to pH and redox, HMSNs were functionalized with cerium and iron oxides. Additionally, they were coated with bacterial-derived exopolysaccharide (EPS) as a biocompatible polymer. In vitro analyses revealed that cytotoxicity induced in cancer cells through oxidative stress, mediated by mature nanocarriers (EPS.IRT.Ce/Fe.HMSN), was surprisingly greater than that caused by free drugs. Cerium and iron ions, in synergy with the drug, were found to generate reactive oxygen species when targeting the acidic pH within lysosomes and the tumor microenvironment. This, in turn, triggered cascade reactions, leading to cell death. In vivo experiments revealed that the proposed nanocarriers had no noticeable effect on healthy tissues. These findings indicate the selective delivery of the drug to cancerous tissue and the induction of antioxidant effects due to the dual catalytic properties of cerium in normal cells. Accordingly, this hybrid drug delivery system provides a more effective treatment for colorectal cancer with the potential for cost-effective scaling up.

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