Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.
Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.
复制标题
DOI：
10.1158/0008-5472.can-17-1655
复制
发表时间：
2017-09
期刊：
影响因子：
11.2
通讯作者：
Yang Zhao;Chenran Zhang;Liquan Gao;Xinhe Yu;Jianhao Lai;D. Lu;Rui Bao;Yanpu Wang;Bing Jia;Fan Wang;Zhaofei Liu
中科院分区：
文献类型：
--
作者：
Yang Zhao;Chenran Zhang;Liquan Gao;Xinhe Yu;Jianhao Lai;D. Lu;Rui Bao;Yanpu Wang;Bing Jia;Fan Wang;Zhaofei Liu
化疗后肿瘤相关巨噬细胞（TAM）向肿瘤募集的增加促进了肿瘤耐药性和复发，并与不良预后相关。TAM消耗抑制肿瘤生长，但由于来自其他基质来源的致瘤介质的作用而不是高度有效的。在这里，我们报告了过继巨噬细胞转移通过增加其肿瘤积累而导致2-（1-己氧基乙基）-2-去乙烯基焦脱镁叶绿酸-α（HPPH）-涂覆的聚乙烯糖基化纳米氧化石墨烯[GO（HPPH）-PEG]的光动力学治疗（PDT）效果显著增强。此外，用常用的化疗药物治疗肿瘤诱导巨噬细胞浸润到肿瘤中的增加，这也增强了肿瘤摄取和GO（HPPH）-PEG的PDT效应，导致肿瘤根除。通过近红外荧光和单光子发射CT成像，使用F4/80特异性成像探针，非侵入性地观察化疗后巨噬细胞向肿瘤的募集。我们的研究结果表明，化疗联合GO（HPPH）-PEG PDT是一种很有前途的策略，用于治疗肿瘤，特别是那些耐化疗的肿瘤。此外，TAM靶向分子成像可能用于预测联合治疗的疗效，并选择最受益于这种治疗方法的患者。Cancer Res; 77（21）; 6021-32.©2017 AACR.
Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR.