A Nitric Oxide (NO) Nanoreporter for Noninvasive Real-Time Imaging of Macrophage Immunotherapy.,Advanced Materials

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A Nitric Oxide (NO) Nanoreporter for Noninvasive Real-Time Imaging of Macrophage Immunotherapy.
Advanced Materials ( IF 27.4 ) Pub Date : 2020-05-11 , DOI: 10.1002/adma.202000648
Anujan Ramesh _{1,

2} , Sahana Kumar ₁ , Anthony Brouillard ₁ , Dipika Nandi ₃ , Ashish Kulkarni _{1,

2,

3,

4}

Affiliation

Macrophage‐centered therapeutic approaches that rely on immune modulation of tumor associated macrophages (TAMs) from a pro‐tumorigenic phenotype (M2) to an anti‐tumorigenic phenotype (M1) have facilitated a paradigm shift in macrophage immunotherapy. However, limited clinical success has been achieved due to the low response rates observed in different types of cancers. The ability to measure immune response in real time is critical in order to differentiate responders from non‐responders; however, there are currently no platforms to monitor real‐time macrophage immunotherapy response. Hence, there is an immediate need to develop imaging techniques that can longitudinally monitor macrophage immunotherapy response. Nitric oxide (NO) produced as a result of activation of macrophages to an anti‐tumorigenic state is considered as a hallmark of M1 and can be a direct indication of response. In this study, a NO nanoreporter (NO‐NR) is reported that enables real‐time monitoring of macrophage immunotherapy drugs in vitro and in vivo. Furthermore, it is observed that sustained inhibition of colony stimulating factor 1 receptor (CSF1R) using a CSF1R inhibitor–NO‐NR system leads to enhanced efficacy and better imaging signal. In conclusion, a first‐of‐its‐kind NO nanoreporter tool is reported that can be used as an activatable imaging agent to monitor macrophage immunotherapy response in real time.

中文翻译：

一氧化氮（NO）纳米报告的巨噬细胞免疫治疗的无创实时成像。

以巨噬细胞为中心的治疗方法依赖于肿瘤相关巨噬细胞（TAM）从原发肿瘤表型（M2）到抗肿瘤发生表型（M1）的免疫调节，促进了巨噬细胞免疫治疗的范式转变。然而，由于在不同类型的癌症中观察到的低响应率，已经取得了有限的临床成功。实时测量免疫反应的能力对于区分反应者和非反应者至关重要。然而，目前尚无监测实时巨噬细胞免疫治疗反应的平台。因此，迫切需要开发可以纵向监测巨噬细胞免疫疗法反应的成像技术。巨噬细胞活化为抗肿瘤发生状态而产生的一氧化氮（NO）被认为是M1的标志，可以直接作为反应的指示。在这项研究中，据报道，NO纳米报告者（NO‐NR）能够在体外和体内实时监测巨噬细胞免疫治疗药物。此外，已观察到使用CSF1R抑制剂-NO-NR系统持续抑制集落刺激因子1受体（CSF1R）可以提高疗效并改善成像信号。总之，据报道，这是首个此类NO纳米报告工具，可以用作可激活的显像剂来实时监测巨噬细胞免疫治疗反应。据报道，NO纳米报告者（NO‐NR）能够在体外和体内实时监测巨噬细胞免疫治疗药物。此外，已观察到使用CSF1R抑制剂-NO-NR系统持续抑制集落刺激因子1受体（CSF1R）可以提高疗效并改善成像信号。总之，据报道，这是首个此类NO纳米报告工具，可以用作可激活的显像剂来实时监测巨噬细胞免疫治疗反应。据报道，NO纳米报告者（NO‐NR）能够在体外和体内实时监测巨噬细胞免疫治疗药物。此外，已观察到使用CSF1R抑制剂-NO-NR系统持续抑制集落刺激因子1受体（CSF1R）可以提高疗效并改善成像信号。总之，据报道，这是首个此类NO纳米报告工具，可以用作可激活的显像剂来实时监测巨噬细胞免疫治疗反应。

更新日期：2020-05-11

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