Document resource
Background Colorectal cancer (CRC), the third most prevalent malignancy globally, faces therapeutic limitations due to its high metastasis rate, chemotherapy resistance, and tumor microenvironment (TME) heterogeneity, which compromise the efficacy of conventional treatments like surgery and chemotherapy.Methods This study developed a multifunctional nanotherapeutic platform by synthesizing mesoporous silica nanoparticles (MSN) via a modified Stöber method ( IDDF2026-ABS-0391 Figure 1. Preparation of MCMG nanoparticles for anti-CRC therapy). The carboxylated MSN surface was sequentially loaded with metformin (Me), chlorin e6 (Ce6), and glucose oxidase (GOX), constructing Me/Ce6@MSN-GOX (MCMG) nanosystem.Results The synthesized MSN exhibited excellent porosity, pore volume, and high loading capacity ( IDDF2026-ABS-0391 Figure 2. Morphological characterization of the nanoparticles). In vitro and in vivo studies demonstrated that MCMG reversed the Warburg effect via the AMPK/ACC/mTOR axis (IDDF2026-ABS-0391 Figure 3), reprogrammed tumor energy metabolism, enhanced Ce6-based photodynamic therapy (PDT) and GOX-induced starvation therapy (IDDF2026-ABS-0391 Figure 4. Characterization of MCMG and its inhibitory effects on colorectal cancer cell migration and invasion, IDDF2026-ABS-0391 Figure 5. In vivo anti-tumor efficacy of MCMG in a subcutaneous HCT116 tumor model). Concurrently, it suppressed HIF-1a expression, alleviated TME hypoxia, and significantly amplified reactive oxygen species generation and tumor cell apoptosis (IDDF2026-ABS-0391 Figure 6. Evaluation of cell viability ROC generation and HIF-1a expression following different treatments).Conclusions This platform integrates metformin’s metabolic regulation, Ce6-mediated, and GO X-driven starvation therapy to achieve synergistic CRC eradication. MCMG enables multifunctional theranostics through synergistic mechanisms (metabolic modulation, oxidative damage and nutrient deprivation) coupled with fluorescence imaging capabilities, offering a novel strategy for CRC treatment.Abstract IDDF2026-ABS-0391 Figure 1Abstract IDDF2026-ABS-0391 Figure 2Abstract IDDF2026-ABS-0391 Figure 3Abstract IDDF2026-ABS-0391 Figure 4Abstract IDDF2026-ABS-0391 Figure 5Abstract IDDF2026-ABS-0391 Figure 6