Visualizing Lysosomal Positioning with a Fluorescent Probe Reveals a New Synergistic Anticancer Effect

Yu, Keke; Ding, Yongsheng; Yu, Hua; Zhu, Wencheng; Yu, Haitao; Luo, Yanju; Zheng, Xujun; Huang, Yan; Lu, Zhiyun; Wang, Xiongjun

doi:10.1021/acssensors.2c00375

Cited by 9 publications

(2 citation statements)

References 28 publications

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“…Adenosine triphosphate (ATP) is a high-energy phosphate compound connected by adenine, ribose, and three phosphate groups, which is called the “energy currency” of the organism. − Lysosome, as a membrane-bound organelle in animal cells, is an important storage place for ATP, and lysosome can respond to external stimuli by exocytosis through releasing ATP. − In the tumor site and microenvironment often accompanied by increased ATP levels, , it is difficult to distinguish ATP in lysosome from ATP in other parts of cells according to previous research . At present, a series of fluorescent probes have been developed to monitor ATP in cells and tissues, but using most of them, the result that only ATP in lysozyme has fluorescence performance cannot be achieved. , The commonly used Zn (DPA) complex has rapid response ability and high sensitivity, but its strong interaction with phosphate groups causes ADP interference and counteracts its specificity to ATP .…”

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confidence: 99%

Three–Four Photon Transition Mn(II) Complex Monitoring Lysosome-Related ATP in Real Time via Fluorescence Lifetime Imaging

Li,

Zhang,

Wang

et al. 2024

Anal. Chem.

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Currently, in situ monitoring of the adenosine triphosphate (ATP) level in lysosomes is critical to understand their involvement in various biological processes, but it remains difficult due to the interferences of limited targeting and low resolution of fluorescent probes. Herein, we report a classic Mn(II) probe (FX2-MnCl 2 ) with near-infrared (NIR) nonlinear (NLO) properties, accompanied by three−four photon transition and fivefold fluorescence enhancement in the presence of ATP. FX2-MnCl 2 combines with ATP through dual recognition sites of diethoxy and manganese ions to reflect slightly fluorescence lifetime change. Through the synergy of multiphoton fluorescence imaging (MP-FI) and multiphoton fluorescence lifetime imaging microscopy (MP-FLIM), it is further demonstrated that FX2-MnCl 2 displays lysosome-specific targeting behavior, which can monitor lysosome-related ATP migration under NIR laser light. This work provides a novel multiphoton transformation fluorescence complex, which might be a potential candidate as a simple and straightforward biomarker of lysosome ATP in vitro for clinical diagnosis.

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confidence: 99%

Three–Four Photon Transition Mn(II) Complex Monitoring Lysosome-Related ATP in Real Time via Fluorescence Lifetime Imaging

Li,

Zhang,

Wang

et al. 2024

Anal. Chem.

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“…Currently, a variety of pH-sensitive uorescent probes already assist in reporting the alterations of the lysosome [9][10][11][12][13][14]. They normally connect to weakly basic subunits and trigger changes in uorescent signal through protonation in the acidic lysosomes.…”

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confidence: 99%

De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation

Huang

Chen

et al. 2022

Preprint

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Background Macroautophagy is an essential cellular self-protection mechanism, and defective autophagy has been considered to contribute to a variety of diseases. During the process, cytoplasmic components are transported via autophagosomes to acidic lysosomes for metabolism and recycling, which represents application niches for lysosome-targeted fluorescent probes. And in view of the complexity of the autophagy pathway, it entails more stringent requirements for probes suitable for monitoring autophagy. Meanwhile, aggregation-induced emission (AIE) fluorescent probes have been impressively demonstrated in the biomedical field, which bring fascinating possibilities to the autophagy visualization. Methods We reported a generalizable de novo design of a novel pH-sensitive AIE probe ASMP-AP tailored to lysosome targeting for the interpretation of autophagy. Firstly, the theoretical calculation was carried out followed by the investigation of optical properties. Then, the performance of ASMP-AP in visualizing autophagy was corroborated by starvation or drugs treatments. Furthermore, the capability of ASMP-AP to monitor autophagy was demonstrated in ex vivo liver tissue and zebrafish in vivo. Results ASMP-AP displays a large stokes shift, great cell permeability and good biocompatibility. More importantly, ASMP-AP enables a good linear response to pH, which derives from the fact that its aggregation state can be manipulated by the acidity. It was successfully applied for imaging autophagy in living cells and was proved capable of monitoring mitophagy. Moreover, this novel molecular tool was validated by ex vivo visualization of activated autophagy in drug-induced liver injury model. Interestingly, it provided a meaningful pharmacological insight that the melanin inhibitor 1-phenyl-2-thiourea (PTU)-induced autophagy was clearly presented in wild-type zebrafish. Conclusions ASMP-AP offers a simple yet effective tool for studying lysosome and autophagy. This is the first instance to visualize autophagy in zebrafish using a small-molecule probe with AIE characters, accurate lysosome targeting and simultaneous pH sensitivity. Ultimately, this novel fluorescent system has great potential for in vivo translation to fuel autophagy research.

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Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects

Cheng,

Qu,

Jiang

et al. 2023

Advanced Materials

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Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor‐specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure‐targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle‐targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug‐related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle‐targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle‐targeting functional materials in precision oncology. We believe that our review will serve as an excellent cutting‐edge guide for researchers in the field of subcellular organelle‐targeted cancer therapy.This article is protected by copyright. All rights reserved

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Visualizing Lysosomal Positioning with a Fluorescent Probe Reveals a New Synergistic Anticancer Effect

Cited by 9 publications

References 28 publications

Three–Four Photon Transition Mn(II) Complex Monitoring Lysosome-Related ATP in Real Time via Fluorescence Lifetime Imaging

Three–Four Photon Transition Mn(II) Complex Monitoring Lysosome-Related ATP in Real Time via Fluorescence Lifetime Imaging

De novo design of a novel AIE fluorescent probe tailored to autophagy visualization via pH manipulation

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects

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