Xu Cheng, Huang Jingsheng, Jiang Yuyan, He Shasha, Zhang Chi, Pu Kanyi
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Nat Biomed Eng. 2023 Mar;7(3):298-312. doi: 10.1038/s41551-022-00978-z. Epub 2022 Dec 22.
Molecular imaging via afterglow luminescence minimizes tissue autofluorescence and increases the signal-to-noise ratio. However, the induction of afterglow requires the prior irradiation of light, which is attenuated by scattering and absorption in tissue. Here we report the development of organic nanoparticles producing ultrasound-induced afterglow, and their proof-of-concept application in cancer immunotheranostics. The 'sonoafterglow' nanoparticles comprise a sonosensitizer acting as an initiator to produce singlet oxygen and subsequently activate a substrate for the emission of afterglow luminescence, which is brighter and detectable at larger tissue depths (4 cm) than previously reported light-induced afterglow. We formulated sonoafterglow nanoparticles containing a singlet-oxygen-cleavable prodrug for the immune-response modifier imiquimod that specifically turn on in the presence of the inflammation biomarker peroxynitrite, which is overproduced by tumour-associated M1-like macrophages. Systemic delivery of the nanoparticles allowed for sonoafterglow-guided treatment of mice bearing subcutaneous breast cancer tumours. The high sensitivity and depth of molecular sonoafterglow imaging may offer advantages for the real-time in vivo monitoring of physiopathological processes.
通过余辉发光进行的分子成像可将组织自发荧光降至最低并提高信噪比。然而，余辉的诱导需要预先用光照射，而光在组织中会因散射和吸收而衰减。在此，我们报告了产生超声诱导余辉的有机纳米颗粒的开发及其在癌症免疫诊疗中的概念验证应用。“声致余辉”纳米颗粒包含一种声敏剂，作为引发剂产生单线态氧，随后激活一种底物以发出余辉发光，这种余辉比先前报道的光诱导余辉更亮，并且在更大的组织深度（4厘米）处可检测到。我们制备了含有免疫反应调节剂咪喹莫特的单线态氧可裂解前药的声致余辉纳米颗粒，该前药在炎症生物标志物过氧亚硝酸盐存在时特异性开启，过氧亚硝酸盐由肿瘤相关的M1样巨噬细胞过度产生。纳米颗粒的全身递送使得能够对患有皮下乳腺癌肿瘤的小鼠进行声致余辉引导治疗。分子声致余辉成像的高灵敏度和深度可能为体内实时监测生理病理过程提供优势。
