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These experimental results showed that the nanosystem effectively improves the tumor microenvironment. This work indicates the great potential of vascular normalization combined with sonodynamic therapy and chemotherapy to enhance efficiency.Immunogene therapy is a novel method for the treatment of colorectal cancer. Cytokine IL-15 has exhibited therapeutic anticancer potential due to its immune-stimulation property. However, conventional IL-15-based cancer gene therapy studies have been performed using the plasmid DNA form, which has