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Precision Navigation of Hepatic Ischemia-Reperfusion Injury Guided by Lysosomal Viscosity-Activatable NIR-II Fluorescence.

ABSTRACT: Hepatic ischemia-reperfusion injury (HIRI) is responsible for postoperative liver dysfunction and liver failure. Precise and rapid navigation of HIRI lesions is critical for early warning and timely development of pretreatment plans. Available methods for assaying liver injury fail to provide the exact location of lesions in real time intraoperatively. HIRI is intimately associated with oxidative stress which impairs lysosomal degradative function, leading to significant changes in lysosomal viscosity. Therefore, lysosomal viscosity is a potential biomarker for the precise targeting of HIRI. Hence, we developed a viscosity-activatable second near-infrared window fluorescent probe (NP-V) for the detection of lysosomal viscosity in hepatocytes and mice during HIRI. A reactive oxygen species-malondialdehyde-cathepsin B signaling pathway during HIRI was established. We further conducted high signal-to-background ratio NIR-II fluorescence imaging of HIRI mice. The contour and boundary of liver lesions were delineated, and as such the precise intraoperative resection of the lesion area was implemented. This research demonstrates the potential of NP-V as a dual-functional probe for the elucidation of HIRI pathogenesis and the direct navigation of HIRI lesions in clinical applications.

SUBMITTER: Liu J

PROVIDER: S-EPMC9354259 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Precision Navigation of Hepatic Ischemia-Reperfusion Injury Guided by Lysosomal Viscosity-Activatable NIR-II Fluorescence.

Liu Jihong J Zhang Wen W Zhou Chunmiao C Li Mengmei M Wang Xin X Zhang Wei W Liu Zhenzhen Z Wu Luling L James Tony D TD Li Ping P Tang Bo B

Journal of the American Chemical Society 20220706 30

Hepatic ischemia-reperfusion injury (HIRI) is responsible for postoperative liver dysfunction and liver failure. Precise and rapid navigation of HIRI lesions is critical for early warning and timely development of pretreatment plans. Available methods for assaying liver injury fail to provide the exact location of lesions in real time intraoperatively. HIRI is intimately associated with oxidative stress which impairs lysosomal degradative function, leading to significant changes in lysosomal vis ...[more]

PMID: 35793548

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Project description:Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. Methods: The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(ɛ-caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR fluorescence activation after accumulation at the tumor site. The activatable nanoplatform was evaluated in vitro and in two different murine cancer models, including an ovarian intraperitoneal metastasis-mimicking model. Furthermore, fluorescence image-guided surgery mediated by this nanoplatform was performed on the employed animal models using a Fluobeam® 800 imaging system. Finally, the phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo. Results: Our in vitro data suggest that the intracellular environment of cancer cells is capable of compromising the integrity of self-assembled nanoparticles and thus causes disruption of the tight dye packing inside the hydrophobic cores and activation of the NIR fluorescence. Animal studies demonstrated accumulation of activatable nanoparticles at the tumor site following systemic administration, as well as release and fluorescence recovery of SiNc from the polymeric carrier. It was also validated that the developed nanoparticles are compatible with the intraoperative imaging system Fluobeam® 800, and nanoparticle-mediated image-guided surgery provides successful resection of cancer tumors. Finally, in vivo studies revealed that combinatorial phototherapy mediated by the nanoparticles could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The revealed properties of the activatable nanoplatform make it highly promising for further application in clinical image-guided surgery and combined phototherapy, facilitating a potential translation to clinical studies.

Dataset Information

Precision Navigation of Hepatic Ischemia-Reperfusion Injury Guided by Lysosomal Viscosity-Activatable NIR-II Fluorescence.

Publications

Precision Navigation of Hepatic Ischemia-Reperfusion Injury Guided by Lysosomal Viscosity-Activatable NIR-II Fluorescence.

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