Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor-associated macrophage in a sorafenib-resistant tumor model.
Inhibition of tumor growth and metastasis by photoimmunotherapy targeting tumor-associated macrophage in a sorafenib-resistant tumor model.
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DOI：
10.1016/j.biomaterials.2016.01.027
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发表时间：
2016-04
期刊：
影响因子：
14
通讯作者：
Chenran Zhang;Liquan Gao;Yuehong Cai;Hao Liu;Duo Gao;Jianhao Lai;Bing Jia;Fan Wang;Zhaofei Liu-Zhaofe
中科院分区：
文献类型：
--
作者：
Chenran Zhang;Liquan Gao;Yuehong Cai;Hao Liu;Duo Gao;Jianhao Lai;Bing Jia;Fan Wang;Zhaofei Liu-Zhaofe
肿瘤相关巨噬细胞（Tumor-associated macrophages，TAMs）在肿瘤侵袭和转移中起重要作用，并导致肿瘤耐药。临床证据表明TAM水平与患者的局部肿瘤复发、远处转移和不良预后相关。在本研究中，我们通过将抗CD 206单克隆抗体与近红外酞菁染料偶联来合成TAM靶向探针（IRD-α CD 206）。然后，我们研究了IRD-α CD 206探针在激酶抑制剂索拉非尼治疗耐药肿瘤的近红外荧光（NIRF）成像和光免疫治疗（PIT）中的潜在应用。索拉非尼治疗对4 T1乳腺癌小鼠模型中的肿瘤生长没有影响，但诱导肿瘤中的M2巨噬细胞极化。通过IRD-α CD 206的体内NIRF成像，对索拉非尼处理的4 T1肿瘤的M2巨噬细胞募集进行了非侵入性可视化。小动物单光子发射型计算机断层扫描（SPECT）/CT和肿瘤内微分布分析表明，经过几轮索拉非尼治疗后，4 T1肿瘤中IRD-α CD 206探针的TAM特异性定位。光照射后，IRD-α CD 206抑制索拉非尼耐药肿瘤的生长。体内CT成像和离体组织学分析证实IRD-α CD 206 PIT抑制小鼠肺转移。这些结果证明了IRD-α CD 206探针用于TAM靶向诊断成像和治疗对传统疗法耐药的肿瘤的实用性。
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-αCD206) by conjugating a monoclonal anti-CD206 antibody with a near-infrared phthalocyanine dye. We then investigated the potential application of the IRD-αCD206 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-αCD206. Small-animal single-photon emission computed tomography (SPECT)/CT and intratumoral microdistribution analysis indicated TAM-specific localization of the IRD-αCD206 probe in 4T1 tumors after several rounds of sorafenib treatment. Upon light irradiation, IRD-αCD206 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-αCD206 PIT. These results demonstrate the utility of the IRD-αCD206 probe for TAM-targeted diagnostic imaging and treatment of tumors that are resistant to conventional therapeutics.