Journal
JOURNAL OF NANOBIOTECHNOLOGY
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12951-022-01526-2
Keywords
Exosomes; Macrophage polarization; Tumor immunity; Mitochondrial functions; Breast cancer
Funding
- National Health and Medical Research Council (NHMRC) Early Career Fellowship [1112258]
- WSU Vice-Chancellor's Senior Research Fellowship
- National Science Foundation of the Jiangsu Higher Education Institutions of China [19KJD350002]
- Jiangsu's Mass Entrepreneurship and Innovation Program
- Natural Science Foundation of Jiangsu Province of China [BK20201443]
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Loading DTX into M1 macrophage-derived exosomes can achieve long-term activation of M1 macrophages in the immunosuppressive tumor microenvironment, leading to improved anti-tumor therapeutic efficacy.
The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naive M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy.
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