Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor-associated macrophage in a sorafenib-resistant tumor model

Tumor-associated macrophages (TAMs) play essential roles in tumor invasion and metastasis, and contribute to drug resistance. Clinical evidence suggests that TAM levels are correlated with local tumor relapse, distant metastasis, and poor prognosis in patients. In this study, we synthesized a TAM-targeted probe (IRD-alpha CD206) by conjugating a monoclonal anti-CD206 antibody with a near-infrared phthalocyanine dye. We then investigated the potential application of the IRD-alpha CD206 probe to near-infrared fluorescence (NIRF) imaging and photoimmunotherapy (PIT) of tumors resistant to treatment with the kinase inhibitor sorafenib. Sorafenib treatment had no effect on tumor growth in a 4T1 mouse model of breast cancer, but induced M2 macrophage polarization in tumors. M2 macrophage recruitment by sorafenib-treated 4T1 tumors was noninvasively visualized by in vivo NIRF imaging of IRD-alpha CD206. Small-animal single-photon emission computed tomography (SPECT)/CT and intratumoral micro distribution analysis indicated TAM-specific localization of the IRD-alpha CD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD-alpha CD206 suppressed the growth of sorafenib-resistant tumors. In vivo CT imaging and ex vivo histological analysis confirmed the inhibition of lung metastasis in mice by IRD-alpha CD206 PIT. These results demonstrate the utility of the IRD-alpha CD206 probe for TAM-targeted diagnostic imaging and treatment of tumors that are resistant to conventional therapeutics. (C) 2016 Elsevier Ltd. All rights reserved."973" program [2013CB733802, 2011CB707705]; National Natural Science Foundation of China [81471712, 81222019, 81125011, 81371614, 81420108019]; Beijing Natural Science Foundation [7132131, 7132123]; Beijing Nova Program [Z121107002512010]SCI(E)EIPubMedARTICLEliuzf@bjmu.edu.cn1-128