A GM-CSF and DOX co-delivery nanoplatform modulates macrophage polarization to promote tumor suppression
Miao Wang,
Jiayu Zhang,
Jiaruo Tang,
Xiaomeng Cai,
Rui Dou,
Chen Guo,
Yi Hu,
Jun Chen
Affiliations
Miao Wang
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China
Jiayu Zhang
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China
Jiaruo Tang
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China
Xiaomeng Cai
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China
Rui Dou
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China
Chen Guo
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China
Yi Hu
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China; State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital, Beijing, 100730, PR China; Corresponding author. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China.
Jun Chen
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Beijing, 100049, PR China; Corresponding author.
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.