Moreover, the effect of the IL-12 pH-responsive NPs was then investigated in the CRC 3D immuno-spheroid model, in which the pH-responsive NPs reduced the expression of the anti-inflammatory CD163 macrophage marker, while increasing the levels of the pro-inflammatory CD86 macrophage marker, hence confirming the ability to reeducate the tumor immune microenvironment. The gene discussed is CD86; the disease is neoplasm.