A Simple Aggregation-Induced Emission Nanoprobe with Deep Tumor Penetration for Hypoxia Detection and Imaging-Guided Surgery in Vivo

Abstract

The pan-cancer detection and precise visualization of tiny tumors in surgery still face great challenges. As tumors grow aggressively, hypoxia is a common feature of solid tumors and has supplied a general way for detecting tumors. Herein, we report a simple aggregation-induced emission nanoprobe-TPE-4NE-O that can specifically switch on their fluorescence in the presence of cytochrome P450 reductase, a reductase which is overexpressed under hypoxia conditions. The probe can selectively light up the hypoxia cells and has shown enhanced deep tumor penetration via charge conversion both in vitro and in vivo. After being modified with FA-DSPE-PEG, higher tumor uptake can be seen and FA-DSPE/TPE-4NE-O showed specific visualization to the hypoxia cancer cells. Excitingly, much brighter fluorescence was accumulated at the tumors in the FA-DSPE/TPE-4NE-O group, even though the tumor was as small as 2.66 mm. The excellent performance of FA-DSPE/TPE-4NE-O in detecting tiny tumors has made it possible for imaging-guided tumor resection. More importantly, the probe exhibited good biocompatibility with negligible organ damage and eliminated a hemolysis risk. The simple but promising probe has supplied a new strategy for pan-cancer detection and tiny tumor visualization, which have shown great potential in clinical translation.

Emission‐Tunable Nanofluorophores through Self‐assembly of Amphiphilic Block Copolymers: toward Application in Cell Imaging

“…[ 30‐33 ] Incorporating AIE fluorophores into amphiphilic molecules to construct water‐soluble aggregates is a feasible way to solve the above problem. [ 34‐40 ] Many fabrication strategies, such as atom transfer radical polymerization (ATRP), reversible addition‐fragmentation chain transfer (RAFT) polymerization, multicomponent reaction (MCR) and surfactant encapsulation, have been developed for the synthesis of water‐soluble AIE fluorescent probes for biomedical applications. [ 41‐43 ] However, drawbacks also exist in these methods.…”

Progresses in Fluorescence Imaging Guidance for Bone and Soft Tissue Sarcoma Surgery

“…One is the activation of intracellular enzymes, such as β-galactosidase bioactivation ( 24 ) and glutathione (GSH) bioactivation ( 25 ). And the other one is the activation of fluorescence by the tumor cell hypoxia environment ( 26 ). Besides, the pH of the tumor microenvironment is generally between 6.7-7.1, the pH of tumor cells is between 5.9-6.2, and the pH of advanced tumor cells can even reach 5.0-5.5, which is an acidic environment compared with normal tissues.…”

Recent Advances in Aggregation‐Induced Emission Materials and Their Biomedical and Healthcare Applications

“…D) Imaging‐guided for the resection of tumors in Hepa1‐6 bearing mice by FA‐DSPE/TPE‐4NE‐O after being intravenously injected for 4 h. Reproduced with permission. [ 92 ] Copyright 2020, American Chemical Society.…”

“…utilized a hypoxia environment‐sensitive AIEgen (TPE‐4NE‐O) that could specifically switch on their fluorescence in the presence of cytochrome P450 reductase to realize the tumor imaging and image‐guided surgery. [ 92,95 ] The probe could selectively light up the hypoxia cells and showed enhanced deep tumor penetration via charge conversion both in vitro and in vivo (Figure 13C). Folic acid‐DSPE‐PEG (FA‐DSPE‐PEG) was applied to encapsulate TPE‐4NE‐O to achieve active tumor targeting ability and specific visualization to the hypoxia cancer cell.…”