Bienzyme-Locked Activatable Fluorescent Probes for Specific Imaging of Tumor-Associated Mast Cells

Abstract

Tumor-associated mast cells (TAMCs) have been recently revealed to play a multifaceted role in the tumor microenvironment. Noninvasive optical imaging of TAMCs is thus highly desired to gain insights into their functions in cancer immunotherapy. However, due to the lack of a single enzyme that is specific to mast cells, a common probe design approach based on single-enzyme activation is not applicable. Herein, we reported a bienzyme-locked molecular probe (THC MC ) based on a photoinduced electron transfer-intramolecular charge-transfer hybrid strategy for in vivo imaging of TAMCs. The bienzyme-locked activation mechanism ensures that THC MC exclusively turns on near-infrared (NIR) fluorescence only in the presence of both tryptase and chymase specifically coexpressed by mast cells. Thus, THC MC effectively distinguishes mast cells from other leukocytes, including T cells, neutrophils, and macrophages, a capability lacking in single-locked probes. Such a high specificity of THC MC allows noninvasive tracking of the fluctuation of TAMCs in the tumor of living mice during cancer immunotherapy. The results reveal that the decreased intratumoral signal of THC MC after combination immunotherapy correlates well with the reduced population of TAMCs, accurately predicting the inhibition of tumor growth. Thus, this study not only presents the first NIR fluorescent probe specific for TAMCs but also proposes a generic bienzymelocked probe design approach for in vivo cell imaging.

Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly

“…The presence of enzymes in the blood may contribute to elevated background signals, reduction of the SBR, or even production of adverse effects in vivo . To address this issue, the use of bienzyme- or multienzyme-activatable E-MISA probes may prove to be an effective strategy for reducing nonspecific background signals and enhancing imaging and/or therapeutic effects in vivo …”

“… 177 To address this issue, the use of bienzyme- or multienzyme-activatable E-MISA probes may prove to be an effective strategy for reducing nonspecific background signals and enhancing imaging and/or therapeutic effects in vivo. 178 …”

A hemicyanine-based near-infrared fluorescent probe with large Stokes shift for non-invasive bioimaging of brown adipose tissue

“…In this study, we rationally designed and synthesized three NIR fluorescent probes ( HCYBAT-1-3 ) based on a hemicyanine scaffold, which has the merits of NIR fluorescence emission and easy functionalization. 34–38 The molecular structure of HCYBAT-1-3 comprised an indolium moiety as the electron acceptor, an ethylene and thiophene fragment as the π-bridge, and a trisubstituted amine segment as the electron donor. The resulting classical D–π–A molecular configuration thereby induced NIR fluorescence emission in the range of 650–900 nm and exhibited a large Stokes shift (over 130 nm) due to the electron push–pull effect.…”