Studies on ferritin based dual functional nanoparticle for tumor associated macrophage targeted for cancer immunotherapy

Abstract

Tumor associated macrophage (TAM) is related to the poor prognosis and chemotherapy resistance in most cancers. TAM promotes cancer cell extravasation, survival and proliferation. TAMs have over-expressed marker CD206, which makes TAMs proper target for cancer immunotherapy through re-polarization of M2-like TAM into M1 type macrophage. Ferritin is a major iron storage protein found in most living organisms. Each ferritin consists of 24 subunits that can self-assemble to form a nanoparticle structure. Surface of ferritin nanoparticle can be genetically modified to present a targeting moiety. Recently, many studies on the surface modified ferritin nanoparticle-based drug delivery systems have been reported. In this study, the ferritin nanoparticle surface was modified to present the CD206 targeting moiety and protamine for gene binding. IRF3 ‘and STAT3 signaling were directly related to the M2 polarization of tumor associated macrophage. Our strategy for cancer immunotherapy is suppressing these two signals through the dual functional ferritin nanoparticle based siIRF3 and Stattic (STAT-3 inhibitor) delivery. Targeting ability of ferritin carrier system to M2-like TAM and the gene expression pattern changes in re-polarized M1 type macrophage through ferritin nanoparticle-based delivery system were successfully verified. Indirect co-culture study showed that re-polarization of M2-like TAM into M1 type has an indirect effect on the down regulated cancer cell proliferation. This dual-functional delivery strategy would be applied to a broad range of combination therapy.