Direct Real‐Time Monitoring of Prodrug Activation by Chemiluminescence

Abstract

The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal-to-noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β-galactosidase. The activation of the prodrug in the presence of β-galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β-galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β-galactosidase-overexpressing tumor-bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment.

Recent Advances and Challenges in Luminescent Imaging: Bright Outlook for Chemiluminescence of Dioxetanes in Water

“…The structure and activation mechanism of this theranostic prodrug are presented in Figure 7A. 56 The prodrug is comprised of a phenoxy-dioxetane luminophore and the antineoplastic drug monomethyl auristatin E (MMAE) and is designed to be activated by β-galactosidase. Following the removal of the phenol masking group by β-galactosidase, 1,6-elimination and decarboxylation take place rapidly to release the active drug and a quinone-methide species.…”

Ultrasensitive Detection of Salmonella and Listeria monocytogenes by Small‐Molecule Chemiluminescence Probes

“…Presumptive colonies have to be confirmed after the initial isolation. [25][26][27][28][29][30][31][32][33][34] Ar emarkable enhancement of light emission was obtained by simply improving the emissive nature of the excited species,f ormed during the chemiexcitation of Schaapsdioxetanes. Positive results are available after 96-144 h(4-6 days), depending on the growth of the bacteria.…”

Chemiluminescence and Bioluminescence Imaging for Biosensing and Therapy: In Vitro and In Vivo Perspectives

“…Then CGKRK peptide was conjugated on the luminophore using a maleimide as linker, which thus increased the aqueous solubility and cell permeability of luminophore under aqueous condition, realizing the first CL microscopy cell-imaging for cathepsin B detection. Besides, other novel luminophores such as CL formaldehyde probes 100, turn-on CL prodrug probes 101 and afterglow luminescent NPs with aggregation induced emission 102 were also synthesized for in vivo biosensing and cancer treatment.…”