Noninvasive Imaging of Tumor Glycolysis and Chemotherapeutic Resistance via De Novo Design of Molecular Afterglow Scaffold

Abstract

Chemotherapeutic resistance poses a significant challenge in cancer treatment, resulting in the reduced efficacy of standard chemotherapeutic agents. Abnormal metabolism, particularly increased anaerobic glycolysis, has been identified as a major contributing factor to chemotherapeutic resistance. To address this issue, noninvasive imaging techniques capable of visualizing tumor glycolysis are crucial. However, the currently available methods (such as PET, MRI, and fluorescence) possess limitations in terms of sensitivity, safety, dynamic imaging capability, and autofluorescence. Here, we present the de novo design of a unique afterglow molecular scaffold based on hemicyanine and rhodamine dyes, which holds promise for low-background optical imaging. In contrast to previous designs, this scaffold exhibits responsive "OFF-ON" afterglow signals through spirocyclization, thus enabling simultaneous control of photodynamic effects and luminescence efficacy. This leads to a larger dynamic range, broader detection range, higher signal enhancement ratio, and higher sensitivity. Furthermore, the integration of multiple functionalities simplifies probe design, eliminates the need for spectral overlap, and enhances reliability. Moreover, we have expanded the applications of this afterglow molecular scaffold by developing various probes for different molecular targets. Notably, we developed a water-soluble pH-responsive afterglow nanoprobe for visualizing glycolysis in living mice. This nanoprobe monitors the effects of glycolytic inhibitors or oxidative phosphorylation inhibitors on tumor glycolysis, providing a valuable tool for evaluating the tumor cell sensitivity to these inhibitors. Therefore, the new afterglow molecular scaffold presents a promising approach for understanding tumor metabolism, monitoring chemotherapeutic resistance, and guiding precision medicine in the future.

Controlled In Situ Self-Assembly of Biotinylated Trans-Cyclooctene Nanoparticles for Orthogonal Dual-Pretargeted Near-Infrared Fluorescence and Magnetic Resonance Imaging

“…P-Cy-TCO&Bio comprises (1) a quenched fluorophore (mCy), (2) a hydrophilic phosphate group (PO 3 H 2 ), (3) a hydrophobic D -dipeptide ( D -FF), (4) a TCO group for bioorthogonal IEDDA reaction, and (5) a biotin at the end (Figure a). We used mCy as the fluorophore because it can emit strong NIR FL at 710 nm via an intermolecular-charge transfer (ICT) process, which has been widely applied in the development of fluorogenic NIR probes for in vivo imaging. − The addition of biotin not only provided P-Cy-TCO&Bio with tumor-targeting ability but also resulted in a strong binding affinity with SA. To ensure efficient in vivo coupling for dual-pretargeted NIR FL and MR imaging, we also designed (1) paramagnetic Tz-Gd as a small-molecule MRI reporter with low r 1 relaxivity and fast IEDDA reaction with the TCO group, and (2) fluorescent SA-780 as a NIR FL reporter that selectively binds to biotin (Figure b).…”

Simultaneously enhancing organic phosphorescence quantum yields and lifetimes for triphenylphosphine salt doped polymer films

“…Organic room temperature phosphorescence (RTP) materials with ultralong emission lifetimes have rapidly developed in recent years due to their great potential in diverse areas including bioimaging, 1–4 X-ray detection, 5–7 and information encryption. 8–10 Achieving high quantum yield and long emission decay time is essential for these applications.…”

A β-Galactosidase-Activated Fluorogenic Reporter for the Detection of Gastric Cancer In Vivo and in Urine

“…Despite CT imaging of the abdomen being considered the routine diagnostic modality, it is insensitive and difficult for detecting tiny lesions such as peritoneal metastases, while X-ray imaging has the risk of exposure to ionizing radiation . Optical imaging offers an indispensable tool for real-time and noninvasive visualization of biological and pathological processes in fundamental research and clinical practice. − Recently, fluorescence imaging techniques have been used in laparoscopic gastrectomy in combination with FDA-approved indocyanine green (ICG) . However, ICG produces “always-on” fluorescence and demonstrates inferior specificity to pathological sites due to the frequent occurrence of false positive results caused by nonspecific interactions .…”