In Vivo Monitoring of Cellular Senescence by Photoacoustic and Fluorescence Imaging Utilizing a Nanostructured Organic Probe
In Vivo Monitoring of Cellular Senescence by Photoacoustic and Fluorescence Imaging Utilizing a Nanostructured Organic Probe
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DOI：
10.1101/2023.07.12.548691
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发表时间：
2023-07
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通讯作者：
Andrew G. Baker;H. Ou;Muhamad Hartono;A. B. Popov;Emma L. Brown;J. Joseph;Monika A Golinska;C. Sanghera;Estela González-Gualda;David Macías;Thomas R. Else;H. Greer;A. Vernet;S. Bohndiek;L. Fruk;D. Muñoz-Espín
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作者：
Andrew G. Baker;H. Ou;Muhamad Hartono;A. B. Popov;Emma L. Brown;J. Joseph;Monika A Golinska;C. Sanghera;Estela González-Gualda;David Macías;Thomas R. Else;H. Greer;A. Vernet;S. Bohndiek;L. Fruk;D. Muñoz-Espín
衰老细胞在包括癌症在内的多种年龄相关疾病中积累，加剧了病理表现，根除这些细胞已成为一种有前途的治疗策略。尽管衰老在疾病中的影响，但由于其次优的特异性、可平移性和组织迁移率，开发用于监测体内衰老负荷的工具仍然是一个挑战。在这里，我们设计了一种纳米结构的有机探针（NanoJaggs）的基础上生物相容性吲哚菁绿色染料（ICG）的积木形成J-聚集体，具有独特的光谱特性，允许荧光和光声层析成像（PAT）检测。我们表明，NanoJaggs被一个活跃的内吞过程吸收，并在几种体外衰老模型中表现出在溶酶体隔室的选择性积累。最后，NanoJagg探针在两项体内研究中得到验证，包括活体PAT成像，与未经治疗的增殖性肿瘤相比，NanoJagg探针对化疗诱导衰老的肿瘤显示出显着的特异性。体外、离体和体内均表明NanoJaggs是用于检测衰老的临床上可转化的工具，并且其稳健的PAT信号使其适合于在化疗或放疗后纵向监测实体肿瘤中的衰老负荷。
Senescent cells accumulate in multiple age-related disorders, including cancer, exacerbating the pathological manifestations, and the eradication of these cells has emerged as a promising therapeutic strategy. Despite the impact of senescence in diseases, the development of tools to monitor the senescent burden in vivo remains a challenge due to their suboptimal specificity, translatability, and tissue penetrance. Here, we have designed a nanostructured organic probe (NanoJaggs) based on biocompatible indocyanine green dye (ICG) building blocks forming J-aggregates, which possess distinct spectral properties allowing both fluorescence and photoacoustic tomography (PAT) detection. We show that NanoJaggs are taken up by an active process of endocytosis and exhibit selective accumulation at the lysosomal compartment in several in vitro models for senescence. Finally, NanoJagg probe is validated in two in vivo studies including live PAT imaging and shows remarkable specificity to tumours with chemotherapy-induced senescence compared to untreated proliferative tumors. In vitro, ex vivo and in vivo all indicate that NanoJaggs are a clinically translatable tool for detection of senescence and their robust PAT signal makes them suitable for longitudinal monitoring of the senescent burden in solid tumors after chemo or radiotherapy.