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Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy
Advanced Science ( IF 15.1 ) Pub Date : 2018-02-26 , DOI: 10.1002/advs.201700891
Jinrong Peng 1 , Yao Xiao 1 , Wenting Li 2 , Qian Yang 3 , Liwei Tan 2 , Yanpeng Jia 1 , Ying Qu 1 , Zhiyong Qian 1
Affiliation  

The therapeutic outcome of photothermal therapy (PTT) remains impeded by the transparent depth of light. Combining PTT with immunotherapy provides strategies to solve this problem. Regulating metabolism‐related enzymes is a promising strategy to stimulate immune response. Here, a nanosystem (NLG919/IR780 micelles) with the properties of photothermal conversion and regulation of the tryptophan metabolic pathway is used to suppress the growth of the tumor margin beyond effective PTT and promote tumor PTT and immunotherapy. It is revealed that mild heat treatment promotes the growth of the tumor margin beyond effective PTT for the upregulation of heat shock protein (HSP), indoleamine 2,3‐dioxygenase (IDO), and programmed death‐ligand 1 (PD‐L1). The NLG919/IR780 micelles can effectively inhibit the activity of IDO but do not affect the level of IDO expression. NLG919/IR780 micelles can effectively accumulate in the tumor and can migrate to lymph nodes and the lymphatic system. In vivo antitumor studies reveal that NLG919/IR780 micelles effectively suppress the growth of tumor margin following PTT in primary tumors. NLG919/IR780 micelle‐mediated PTT and IDO inhibition further stimulate the activation of T lymphocytes, inhibiting the growth of distal tumors (abscopal effect). The results demonstrate that the NLG919/IR780 micelles combine PTT and immunotherapy and suppress the tumor margin as well as distal tumor growth post photothermal therapy.

中文翻译:

光敏胶束与IDO抑制剂一起增强癌症的光热疗法和免疫疗法

光热疗法(PTT)的治疗结果仍然受到透明光深度的阻碍。PTT与免疫疗法的结合提供了解决此问题的策略。调节与代谢相关的酶是刺激免疫反应的一种有前途的策略。在这里,具有光热转化和色氨酸代谢途径调节特性的纳米系统(NLG919 / IR780胶束)被用于抑制肿瘤边缘的生长,超出有效的PTT范围,并促进肿瘤PTT和免疫疗法。揭示了温和的热处理会促进肿瘤边缘的生长,超出有效PTT的表达,从而上调热休克蛋白(HSP),吲哚胺2,3-二加氧酶(IDO)和程序性死亡配体1(PD-L1)。NLG919 / IR780胶束可有效抑制IDO的活性,但不影响IDO表达的水平。NLG919 / IR780胶束可以有效地积聚在肿瘤中,并可以迁移到淋巴结和淋巴系统。体内抗肿瘤研究表明NLG919 / IR780胶束可有效抑制原发肿瘤中PTT后肿瘤边缘的生长。NLG919 / IR780胶束介导的PTT和IDO抑制作用进一步刺激T淋巴细胞的活化,从而抑制远端肿瘤的生长(绝对作用)。结果表明,NLG919 / IR780胶束结合了PTT和免疫疗法,并抑制了光热疗法后的肿瘤边缘以及远端肿瘤的生长。体内抗肿瘤研究表明NLG919 / IR780胶束可有效抑制原发肿瘤中PTT后肿瘤边缘的生长。NLG919 / IR780胶束介导的PTT和IDO抑制作用进一步刺激T淋巴细胞的活化,从而抑制远端肿瘤的生长(绝对作用)。结果表明,NLG919 / IR780胶束结合了PTT和免疫疗法,并抑制了光热疗法后的肿瘤边缘以及远端肿瘤的生长。体内抗肿瘤研究表明NLG919 / IR780胶束可有效抑制原发肿瘤中PTT后肿瘤边缘的生长。NLG919 / IR780胶束介导的PTT和IDO抑制作用进一步刺激T淋巴细胞的活化,从而抑制远端肿瘤的生长(绝对作用)。结果表明,NLG919 / IR780胶束结合了PTT和免疫疗法,并抑制了光热疗法后的肿瘤边缘以及远端肿瘤的生长。
更新日期:2018-02-26
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