Polymeric Nanoparticles Induce NLRP3 Inflammasome Activation and Promote Breast Cancer Metastasis

Abstract Polymeric nanoparticles gain enormous interests in cancer therapy. Polyethylenimine (PEI) 25 kD is well known for its high transfection efficiency and cytotoxicity. PEI‐CyD (PC) was previously synthesized by conjugating low molecular PEI ( M w 600) with β‐cyclodextrin (β‐CyD), which is shown to induce lower cytotoxicity than PEI 25 kD. In the current study, the in vivo immune response of branched PEI 25 kD and PC is investigated. Compared to PC/pDNA, exposure of PEI 25kD/pDNA induces higher level of immune‐stimulation evidenced by the increased spleen weight, phagocytic capacity of peritoneal macrophage, and proinflammatory cytokines in serum and liver. Importantly, administration of PEI 25 kD can greatly promote breast cancer metastasis in liver and lung tissues, which correlates with its ability to induce high oxidative stress and NLRP3‐inflammasome activation. These results suggest that polymeric nanocarriers have the potential to induce immune‐stimulation and cancer metastasis, which may affect their efficiency for cancer therapy.