RGD-modified hollow mesoporous nanoparticles loaded with cisplatin for antitumor therapy in colon cancer

To develop an Arg-Gly-Asp peptide (RGD)-targeted hollow mesoporous manganese dioxide nanoparticle system loaded with cisplatin (RGD-HMnO₂/CDDP) and evaluate its in vitro antitumor activity, in vivo therapeutic efficacy, and mechanisms in colon cancer. Hollow MnO₂ (HMnO₂) was fabricated using SiO₂ nanospheres as a hard template via KMnO₄ oxidative deposition followed by Na₂CO₃ etching. Cisplatin was loaded and RGD peptides were conjugated to obtain RGD-HMnO₂/CDDP. Morphology and physicochemical properties were characterized by TEM, XRD, XPS, DLS, and zeta potential. In CT26 cells, cytotoxicity (CCK-8), invasion/migration (Transwell), reactive oxygen species (ROS, DCFH-DA), mitochondrial membrane potential (JC-1), DNA damage (γ-H2AX), apoptosis (Western blot; Annexin V-FITC/PI) were assessed. In tumor-bearing mice, antitumor efficacy, serum cytokines (TNF-α, IFN-γ, IL-6, IL-2, IL-10), and hematological indices were evaluated. RGD-HMnO₂/CDDP showed markedly enhanced cytotoxicity versus free cisplatin and non-targeted HMnO₂/CDDP, and significantly inhibited invasion and migration. Mechanistically, it increased intracellular ROS, induced mitochondrial depolarization, elevated γ-H2AX, and activated apoptosis signaling, resulting in higher apoptotic rates. In vivo, RGD-HMnO₂/CDDP achieved superior tumor growth inhibition, modulated inflammatory/immune cytokines, and maintained favorable hematological profiles, indicating good immunomodulation and biocompatibility. RGD-HMnO₂/CDDP enhances cisplatin efficacy against colon cancer by promoting ROS-driven mitochondrial dysfunction and DNA damage–associated apoptosis, with potential improvement of the tumor immune microenvironment and without compromising systemic safety.