Dataset Information

Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging.

ABSTRACT: Construction of tumor microenvironment responsive probe with more than one imaging modality, in particular toward hypoxia of solid tumors, is an appealing yet significantly challenging task. In this work, we designed a hypoxia-activated probe TBTO (Triphenylamine-Benzothiadiazole-Triphenylamine derivative featuring four diethylamino N-Oxide groups) for in vivo imaging. TBTO could undergo bioreduction in a hypoxic microenvironment to yield compound TBT sharing both near-infrared (NIR) aggregation-induced emission and strong twisted intramolecular charge transfer features, which endows the probe with excellent performance in NIR fluorescence and photoacoustic dual-mode tumor imaging. This study offers useful insights into designing a new generation agent for clinical cancer diagnosis.

SUBMITTER: Li M

PROVIDER: S-EPMC7973868 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging.

Li Meng M Li Huan H Wu Qian Q Niu Niu N Huang Jiachang J Zhang Lingmin L Li Ying Y Wang Dong D Tang Ben Zhong BZ

iScience 20210302 3

Construction of tumor microenvironment responsive probe with more than one imaging modality, in particular toward hypoxia of solid tumors, is an appealing yet significantly challenging task. In this work, we designed a hypoxia-activated probe TBTO (Triphenylamine-Benzothiadiazole-Triphenylamine derivative featuring four diethylamino N-Oxide groups) for <i>in vivo</i> imaging. TBTO could undergo bioreduction in a hypoxic microenvironment to yield compound TBT sharing both near-infrared (NIR) aggr ...[more]

PMID: 33763638

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Project description:Tumor microenvironment (TME)-activated theranostics is a promising strategy to effectively identify small lesions, improve antitumor efficacy, and reduce the risk of undesired side effects. Hypoxia, as a common characteristic of TME, can serve as a preferred site for stimulus-dependent activation; however, tumor-hypoxia levels in various developmental stages exhibit different characteristics, severely limiting the response sensitivity. Herein, a circulating self-reinforcing hypoxic nanoamplifier (CGH NAs) is developed that utilizes a dual-chain reaction process (internal regulation, internal regulation) to achieve precise activation of NIR-II FL/photoacoustic (PA) imaging-guided synergistic therapy. Inspired by the positive correlation of nitroreductase (NTR) with hypoxia, the CGH NAs encapsulate CQ4T and GOx into NTR-sensitive hyaluronic acid-nitroimidazole (HA-NI) shell via a self-assembly approach, enabling aggregation-caused NIR-II FL quenching and tumor-accurate delivery. When CGH NAs efficiently accumulated in the tumor region, the intensive local NTR reduced hydrophobic –NO2 to hydrophilic –NH2, which lead to disassembly of CGH NAs. The released GOx could consume O2 (internal regulation) and glucose to cut off the energy supply, inducing tumor-starvation therapy; generate gluconic acid and H2O2 (oxidative stress). Meanwhile, the released CQ4T promoted rapid recovery of NIR-II FL signals for imaging-guided PDT, which could simultaneously deplete intratumoral O2 (external stimulation). Remarkably, the strengthened tumor-hypoxia levels in turn accelerated the NTR-responsive degradation of the CGH NAs, thereby achieving high-efficiency theranostic. Graphical abstract In this work, a novel “internal regulation, internal regulation” dual sensitization strategy to construct a cyclically enhanced NTR-responsive nanoamplifier CGH NAs for achieving activatable NIR-Ⅱ NIR-II FL/PA imaging-guided oxidative stress/starvation/PDT combination therapy is designed. The dual-chain reaction process could in situ aggravated the hypoxic levels to enhance the NTR-response activity in the tumor region effectively, which might represent a promising intelligent nanomedicine in precision cancer theranostics.Image 1 Highlights • The cyclically enhanced NTR-responsive CGH NAs possess a dual sensitization strategy for precision tumor theranostics.• The CGH NAs utilize the “internal regulation and external stimulation” dual-mechanism to amplify the hypoxia response cyclically, realizing a self-promoting degradation process.• The enhanced intratumoral hypoxia levels can positively feedback-regulate to achieve precise release of GOx and CQ4T for “turn on” NIR-II FL imaging and oxidative stress/starvation/PDT combination therapy.

Dataset Information

Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging.

Publications

Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging.

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