Organelle-Partitioned Sugar–Rhodamine Diad for In Vivo Tumor Imaging

Abstract

Current tumor imaging agents are often limited by their liability to dissipate from tumor tissues. As cell sugar sorting enables exogenous sugars to be delivered into predetermined subcellular locations, we synthesized sialic acid (Sia) derivatives with rhodamine-X conjugated at C-9 ( ROX Sia), which hitchhikes cell sialic acid sorting to target tumor cell lysosomes, exhibiting pH-independent long-term probe retention in lysosomes. ROX Sia gives selective, bright, and endured fluorescence signals in subcutaneous tumors and orthotopic tumors in mice models. These results indicate the potential of ROX Sia as a lysosome-targeted optical agent for fluorescence-guided tumor resection.

γ‐Glutamyltranspeptidase (GGT)‐Activatable Fluorescence Probe for Durable Tumor Imaging

“…Further, in order to perform histopathological or immunohistochemical diagnosis of the resected fluorescent regions, the fluorescent signal should be resistant to fixation and compatible with immunohistochemical staining. Others have used tumor‐targeting glycans (for lysosomal retention) to induce long‐term fluorescence signals, but these would not be resistant to fixation as they do not form a covalent bond [6] . Also, some fluorescently quenched activity‐based probes (qABPs) for cysteine cathepsins [7] have been reported to form fluorescent adducts with the target enzymes, providing a durable signal in vivo, but these suicide substrate probes form covalent bonds with active site nucleophiles, resulting in loss of the enzyme activity.…”

γ‐Glutamyltranspeptidase (GGT)‐Activatable Fluorescence Probe for Durable Tumor Imaging

“…Others have used tumor-targeting glycans (for lysosomal retention) to induce long-term fluorescence signals, but these would not be resistant to fixation as they do not form a covalent bond. [6] Also, some fluorescently quenched activity-based probes (qABPs) for cysteine cathepsins [7] have been reported to form fluorescent adducts with the target enzymes, providing a durable signal in vivo, but these suicide substrate probes form covalent bonds with active site nucleophiles, resulting in loss of the enzyme activity. Thus, amplification by enzymatic turnover cannot be expected.…”