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

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.

Microwave-Assisted Synthesis of the Red-Shifted Pentamethine Tetrahydroxanthylium Core with Absorbance within the Near Infrared-II Window

“…The other side of the fluorophores does not contribute to the total energy of the molecule at the ground state. It is already known that conjugation within the polymethine chain in most contrast agents results in the delocalization of electrons, which results in positive charge distribution within the terminal heterocycles. ,, Interestingly, the ground state energies of compounds 4 and 11 tend to be roughly the same despite the difference in the central meso position fragments. However, compound 6 bearing the bromine atom at the meso position has the lowest ground state energy.…”

AcGlcAs: A Novel P53-Targeting Arsenical with Potent Cellular Uptake and Cancer Cell Selectivity

“…We next determined whether passive diffusiona process that does not consume energyis a contributing factor to the cellular uptake of AcGlcAs. A well-established experimental approach was employed, wherein active cellular uptake pathways were selectively obstructed through incubation at 4 °C. − As compared to the standard 37 °C incubation, 4 °C incubation dramatically impaired the cellular uptake of As upon both 1 and 10 μM AcGlcAs treatment in HepG2 cells (Figure K), suggesting that an active cellular uptake pathway, presumably the thiol-mediated pathway, is the major cell uptake pathway of AcGlcAs.…”

P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging

“…P800SO3-Cl and P800SO3-PEG showed around 40% PPB, while P800SO3 and P800SO3-SH bound significantly to plasma proteins (> 70%). These PPB data are useful to predict the biodistribution and clearance of injected doses in the body [ 31 , 32 ]. We also measured the photostability of these NIR fluorophores at different concentrations (10–100 µM) by irradiating them using an 808 nm laser at a power density of 35 mW/cm 2 for 2 h under the home-built NIR-II imaging system (Fig.…”