Ratiometric Fluorescent Detection of Ultrasound-Regulated ATP Release: An Ultrasound-Resistant Cu,N-Doped Carbon Nanosphere

Zhezhu Nan, Hengyu Liu, Linrong Shi, Hongrui Zhu, Junjie Chen, Tali Ilovitsh, Daocheng Wu, Mingxi Wan, Yi Feng

Research output: Contribution to journalArticlepeer-review

Abstract

Focused ultrasound, as a protocol of cancer therapy, might induce extracellular adenosine triphosphate (ATP) release, which could enhance cancer immunotherapy and be monitored as a therapeutic marker. To achieve an ATP-detecting probe resistant to ultrasound irradiation, we constructed a Cu/N-doped carbon nanosphere (CNS), which has two fluorescence (FL) emissions at 438 and 578 nm to detect ultrasound-regulated ATP release. The addition of ATP to Cu/N-doped CNS was conducted to recover the FL intensity at 438 nm, where ATP enhanced the FL intensity probably via intramolecular charge transfer (ICT) primarily and hydrogen-bond-induced emission (HBIE) secondarily. The ratiometric probe was sensitive to detect micro ATP (0.2-0.6 μM) with the limit of detection (LOD) of 0.068 μM. The detection of ultrasound-regulated ATP release by Cu,N-CNS/RhB showed that ATP release was enhanced by the long-pulsed ultrasound irradiation at 1.1 MHz (+37%, p < 0.01) and reduced by the short-pulsed ultrasound irradiation at 5 MHz (−78%, p < 0.001). Moreover, no significant difference in ATP release was detected between the control group and the dual-frequency ultrasound irradiation group (+4%). It is consistent with the results of ATP detection by the ATP-kit. Besides, all-ATP detection was developed to prove that the CNS had ultrasound-resistant properties, which means it could bear the irradiation of focused ultrasound in different patterns and detect all-ATP in real time. In the study, the ultrasound-resistant probe has the advantages of simple preparation, high specificity, low limit of detection, good biocompatibility, and cell imaging ability. It has great potential to act as a multifunctional ultrasound theranostic agent for simultaneous ultrasound therapy, ATP detection, and monitoring.

Original languageEnglish
Pages (from-to)32732-32743
Number of pages12
JournalACS applied materials & interfaces
Volume15
Issue number27
DOIs
StatePublished - 12 Jul 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

Keywords

  • cell imaging
  • intramolecular charge transfer
  • ratiometric fluorescent carbon nanosphere
  • ultrasound-regulated ATP release
  • ultrasound-resistant probe

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