Targeted MIP-3β plasmid nanoparticles induce dendritic cell maturation and inhibit M2 macrophage polarisation to suppress cancer growth

Abstract

In recent decades, cancer immunotherapy has demonstrated considerable clinical advantages in cancer therapy. Particularly, the use of immunological gene therapy continues to grow in this field. Macrophage Inflammatory Protein 3 Beta (MIP-3β) has emerged as a potential immunomodulator for anti-cancer treatments by enhancing the interaction among immune responses. In this study, we demonstrate an innovative targeted gene delivery system based on a self-assembly technique with 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP), Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA), and folic acid modified poly(ethylene glycol)-poly(ε-caprolactone) (FA-PEG-PCL) (FDMCA). Results showed that the expression of MIP-3β was up-regulated in cancer cells following the transfection with FDMCA-pMIP-3β, in comparison with cells transfected with DMCA-pMIP-3β. The supernatants collected from cancer cells transfected with FDMCA-pMIP-3β and DMCA-pMIP-3β both instigate dendritic cell maturation, M1 polarisation of macrophages, activation and presentation of cytotoxicity in lymphocytes. Moreover, tumor growth and metastasis were markedly inhibited following the administration of the FDMCA-pMIP-3β complex in both subcutaneous and pulmonary metastasis mice models, which is attributed to reduced angiogenesis, enhanced cancer cell apoptosis, and suppressed proliferation by activation of the immune system. Our study suggests that the MIP-3β plasmid and FDMCA complex provide a new approach for the treatment of breast cancer.