A GM-CSF and DOX co-delivery nanoplatform modulates macrophage polarization to promote tumor suppression

Abstract

The immunosuppressive tumor microenvironment often compromises chemotherapeutic efficacy. Tumor-associated macrophages (TAM) are a critical component of the tumor immune microenvironment, a large portion of which is in M2-polarization with immunosuppressive effects. Priming the TAM to M1 polarization is a promising strategy for reversing the immunosuppressive microenvironment for promoting tumor therapy. In this study, a co-delivery nanoplatform that integrates GM-CSF as an immune adjuvant with chemotherapy of DOX has been developed to enhance the efficacy of cancer therapy. The photothermal effect from embedded single-walled carbon nanotubes (SWCNTs) controlled the release of GM-CSF and DOX. The results of MB49 ​cells verified that the GM-CSF pre-treating macrophages enhanced the anti-proliferative efficacy of DOX. This improvement could be related to GM-CSF inducing macrophages to release TNF-α and other cytokines that prevent the growth of cancer cells. This work provides a facile method to prepare a protein/drug/hyperthermia co-delivery system, promising in cancer combined therapy through reversing the immunosuppressive tumor microenvironment.

Keywords

• Granulocyte-macrophage colony stimulating factor (GM-CSF)
• DOX
• Chemotherapy
• Tumor immunity
• Macrophage