Journal
NATURE BIOMEDICAL ENGINEERING
Volume 7, Issue 3, Pages 298-312Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41551-022-00978-z
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Molecular imaging via afterglow luminescence is improved by using organic nanoparticles that produce ultrasound-induced afterglow. These sonoafterglow nanoparticles have higher brightness and detection capabilities at larger tissue depths compared to light-induced afterglow. They were successfully applied in cancer immunotheranostics, allowing for real-time in vivo monitoring of physiopathological processes.
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.
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