Abstract
Background: Postoperative recurrence remains a major challenge in colorectal cancer due to residual tumor cells that survive surgical resection. Systemic chemotherapy is often insufficient for complete local control and causes systemic toxicity. Combining local chemotherapy with gene silencing may offer a more effective and targeted strategy. Methods: We developed PLGA-based nanoparticles co-loaded with irinotecan and Bcl-2-targeting siRNA. The nanoparticles were characterized for morphology, encapsulation efficiency, release kinetics, cellular uptake, cytotoxicity, gene silencing efficiency, and in vivo efficacy using a murine tumor resection model. Results: The dual-loaded nanoparticles exhibited uniform spherical morphology, high encapsulation efficiencies (82.3% for irinotecan and 69.5% for siRNA), and sustained release of both agents. Conclusion: This localized combinatorial delivery system provides a synergistic approach for eliminating residual tumor cells and preventing recurrence after colorectal cancer surgery, demonstrating high therapeutic potential and translational value.
Keywords: Colorectal cancer; postoperative therapy; nanoparticles; siRNA; Bcl-2; local drug delivery; irinotecan