Immunostimulatory effects of IL-12 targeted pH-responsive nanoparticles in macrophage-enriched 3D immuno-spheroids in vitro model

Research Overview

Metastatic colorectal cancer has a five-year survival of only 14%, and immunotherapy has not improved it — partly because the slightly acidic (~pH 6.5) tumor microenvironment is immunosuppressive. Interleukin-12 can reverse that suppression by inducing interferon-gamma, but systemic side effects have blocked its clinical use.

This study developed pH-responsive polymeric nanoparticles that encapsulate IL-12 and release it preferentially in the acidic tumor environment. At pH ~6.5 the IL-12-loaded particles induced an antitumoral pro-inflammatory response in macrophages — higher interferon-gamma and nitric-oxide release — without affecting the cells’ metabolic activity, whereas the response differed at neutral pH.