Enzyme‐Mediated In Situ Self‐Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging

Abstract

Pretargeted imaging has emerged as ap romising approach to advance nuclear imaging of malignant tumors. Herein, we combine the enzyme-mediated fluorogenic reaction and in situ self-assembly with the inverse electron demand Diels-Alder (IEDDA) reaction to develop an activatable pretargeted strategy for multimodality imaging. The transcyclooctene (TCO) bearing small-molecule probe, P-FFGd-TCO,can be activated by alkaline phosphatase and in situ selfassembles into nanoaggregates (FMNPs-TCO)retained on the membranes,p ermitting to (1) amplify near-infrared (NIR) fluorescence (FL) and magnetic resonance imaging (MRI) signals,and (2) enrich TCOs to promote IEDDAligation. The Gallium-68 ( 68 Ga) labeled tetrazine can readily conjugate the tumor-retained FMNPs-TCO to enhance radioactivity uptake in tumors.S trong NIR FL, MRI, and positron emission tomography (PET) signals are concomitantly achieved,allowing for pretargeted multimodality imaging of ALP activity in HeLa tumor-bearing mice.

NIRII‐HDs: A Versatile Platform for Developing Activatable NIR‐II Fluorogenic Probes for Reliable In Vivo Analyte Sensing

“…[20] Further, alkaline phosphatase has been used as a marker to identify cancer cells and tissues. [21] Prior to the using for NIR-II bioimaging in vivo, we investigated the three newly developed NIR-II activatable probes for their corresponding analytes in vitro. As shown in Figure 4b and c, owing to the effectively suppressed electron-donating ability as the hydroxyl decorated, probe NIRII-HD5-ONOO À not only showed nearly no fluorescence when excited with the 808 nm laser but also displayed a significantly blue-shifted absorption peak (λ abs = 723 nm) compared with its original dye NIRII-HD5 (λ abs = 854 nm).…”

Recent Advances in Pretargeted Imaging of Tumors in Vivo

“…Apart from pretargeted fluorescence or PET imaging of tumor apoptosis using the caspase-3/7-controlled in situ selfassembly, Ye and co-workers have recently reported an alkaline phosphatase (ALP) activatable probe (P-FFGd-TCO) for pretargeted multimodal imaging of tumors by leveraging fluorogenic reaction-driven in situ self-assembly and fast IEDDA reaction. [60] P-FFGd-TCO was designed to contain a lipophilic NIR fluorophore (merocyanine, Cy-Cl) caged with a hydrophilic phosphate group, a hydrophilic magnetic DOTA-Gd chelate, a hydrophobic dipeptide (FF) linker and a TCO handle for the IEDDA reaction. P-FFGd-TCO was initially a water soluble probe with"off" NIR FL and a relatively low r 1 relaxivity.…”

Novel YOF-Based Theranostic Agents with a Cascade Effect for NIR-II Fluorescence Imaging and Synergistic Starvation/Photodynamic Therapy of Orthotopic Gliomas

“…Therefore, the early diagnosis of malignant gliomas is particularly significant. Presently commonly used imaging methods for glioblastoma diagnosis mainly include positron emission tomography (PET), magnetic resonance imaging (MRI), single-photon-emission computed tomography (SPECT), and near-infrared (NIR) fluorescence imaging. , In recent years, NIR fluorescence imaging, especially in the second biological window (NIR-II FL), has been given much more consideration owing to its strengths of high sensitivity and spatiotemporal resolution, deep penetration, noninvasiveness, and low background noise. − Many kinds of probes have been explored as candidates for NIR-II FL in vivo until now, such as organic molecules, quantum dots, rare-earth fluorescent nanoparticles, and single-walled carbon nanotubes. − Among them, the rare-earth fluorescent nanoparticles are particularly fascinating owing to the exclusive optical properties, including large Stokes, narrow full width at half-maximum, and tunable excitation and emission, as well as good photostability. − Lanthanide oxyfluorides (LnOF, Ln = Y) nanocrystals with the characters of both fluorides and oxides (i.e., low phonon energy, good optical transparency, and chemical stability) exhibit good potential to act as promising probe for NIR-II FL. − Moreover, Nd 3+ ions with relatively large cross sections could serve as good sensitizer for efficient NIR-II emission excited by 808 nm laser through a self-sensitization process. , Therefore, the Nd 3+ -doped YOF fluorescent nanoparticles would be promising candidates for NIR-II FL of orthotopic glioma in vivo.…”