Dataset Information

Activatable Hybrid Polyphosphazene-AuNP Nanoprobe for ROS Detection by Bimodal PA/CT Imaging.

ABSTRACT: Overproduction of reactive oxygen species (ROS) is often related to inflammation or cancer and can cause tissue damage. Probes that have been previously reported to image ROS typically rely on imaging techniques that have low depth penetration in tissue, thus limiting their use to superficial disease sites. We report herein a novel formulation of hybrid nanogels loaded with gold nanoparticles (AuNP) to produce contrast for computed tomography (CT) and photoacoustics (PA), both being deep-tissue imaging techniques. The polyphosphazene polymer has been designed to selectively degrade upon ROS exposure, which triggers a switch-off of the PA signal by AuNP disassembly. This ROS-triggered degradation of the nanoprobes leads to a significant decrease in the PA contrast, thus allowing ratiometric ROS imaging by comparing the PA to CT signal. Furthermore, ROS imaging using these nanoprobes was applied to an in vitro model of inflammation, that is, LPS-stimulated macrophages, where ROS-triggered disassembly of the nanoprobe was confirmed via reduction of the PA signal. In summary, these hybrid nanoprobes are a novel responsive imaging agent that have the potential to image ROS overproduction by comparing PA to CT contrast.

SUBMITTER: Bouche M

PROVIDER: S-EPMC7039041 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Activatable Hybrid Polyphosphazene-AuNP Nanoprobe for ROS Detection by Bimodal PA/CT Imaging.

Bouché Mathilde M Pühringer Manuel M Iturmendi Aitziber A Amirshaghaghi Ahmad A Tsourkas Andrew A Teasdale Ian I Cormode David P DP

ACS applied materials & interfaces 20190801 32

Overproduction of reactive oxygen species (ROS) is often related to inflammation or cancer and can cause tissue damage. Probes that have been previously reported to image ROS typically rely on imaging techniques that have low depth penetration in tissue, thus limiting their use to superficial disease sites. We report herein a novel formulation of hybrid nanogels loaded with gold nanoparticles (AuNP) to produce contrast for computed tomography (CT) and photoacoustics (PA), both being deep-tissue ...[more]

PMID: 31321973

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Project description:Purpose: A successful cancer surgery requires the complete removal of cancerous tissue, while also sparing as much healthy, non-cancerous tissue as possible. To achieve this, an accurate identification of tumor boundaries during surgery is critical, but intra-operative tumor visualization remains challenging. Fluorescence imaging is a promising method to improve tumor detection and delineate tumor boundaries during surgery, but the lack of stable, long-circulating, clinically-translatable fluorescent probes that can identify tumors with high signal-to-noise ratios and low background fluorescence signals have prevented its widespread application. Methods: We screened the optical properties of several fluorescent dyes before and after nanoprobe encapsulation, and then identified nanoprobes with quenched fluorescence that were re-activated upon dye release. The physical and biological properties of these nanoprobes leading to fluorescence activation were investigated in vitro. Further, the cancer imaging properties of both free dyes and nanoprobe-encapsulated dyes were compared in vivo. Results: A novel fluorescent nanoprobe was prepared by combining two FDA-approved agents commonly used in the clinic: Feraheme (FH) and indocyanine green (ICG). The resulting FH-entrapped ICG nanoprobe [FH(ICG)] displayed quenched fluorescence compared to other nanoprobes, and this quenched fluorescence was re-activated in acidic tumor microenvironment conditions (pH 6.8) and upon uptake into cancer cells. Finally, in vivo studies in a prostate cancer mouse model demonstrated that FH(ICG) treatments enhance long-term fluorescence signals in tumors compared to ICG treatments, allowing for fluorescence-guided tumor identification using clinically relevant fluorescence cameras. Conclusions: FH(ICG) nanoprobes were identified as fluorescent nanoprobes with beneficial fluorescence activation properties compared to other FH-entrapped dyes. The activatable nature of this nanoprobe allows for a low background fluorescence signal and high signal-to-noise ratio within a long-circulating nanoagent, which allows for long-term fluorescence signals from tumors that enabled their fluorescence-guided detection. This activatable nanoprobe offers tremendous potential as a clinically translatable image-guided cancer therapy modality that can be prepared in a clinical setting.

Dataset Information

Activatable Hybrid Polyphosphazene-AuNP Nanoprobe for ROS Detection by Bimodal PA/CT Imaging.

Publications

Activatable Hybrid Polyphosphazene-AuNP Nanoprobe for ROS Detection by Bimodal PA/CT Imaging.

Similar Datasets

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