Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer

Autor: Shinya Yokomizo, Maged Henary, Emmanuel R. Buabeng, Takeshi Fukuda, Hailey Monaco, Yoonji Baek, Sophia Manganiello, Haoran Wang, Jo Kubota, Amy Daniel Ulumben, Xiangmin Lv, Cheng Wang, Kazumasa Inoue, Masahiro Fukushi, Homan Kang, Kai Bao, Satoshi Kashiwagi, Hak Soo Choi
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Advanced Science, Vol 9, Iss 20, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202201416
Popis: Abstract Fluorescence‐guided surgery (FGS) aids surgeons with real‐time visualization of small cancer foci and borders, which improves surgical and prognostic efficacy of cancer. Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH‐sensitive near‐infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported. After topical application of PH08 on peritoneal tumor regions in ovarian cancer‐bearing mice, a rapid fluorescence increase (< 10 min), and extended preservation of signals (> 4 h post‐topical application) are observed, which together allow for the visualization of submillimeter tumors with a high tumor‐to‐background ratio (TBR > 5.0). In addition, PH08 is preferentially transported to cancer cells via organic anion transporter peptides (OATPs) and colocalizes in the mitochondria and lysosomes due to the positive charges, enabling a long retention time during FGS. PH08 not only has a significant impact on surgical and diagnostic applications but also provides an effective and scalable strategy to design therapeutic agents for a wide array of cancers.
Databáze: Directory of Open Access Journals
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