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Issue 40, 2019
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Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide

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Abstract

Elevated levels of intracellular hydrogen peroxide (H2O2) are closely related to the development of cancers. Specific imaging of H2O2 in tumor sites would be significant not only for cancer diagnosis but also for gaining a deep understanding of the role of H2O2 in cancer. However, traditional fluorescent probes based only on responses to overexpression levels of H2O2 in cancer cells are insufficient to distinguish cancer cells from other unhealthy or healthy cells in complex biological systems. Herein, we developed a smart, two-photon fluorescent GC–NABP nanoprobe with pH-dependent surface charge conversion for tumor-targeted imaging of H2O2. The nanoprobe was constructed by the self-assembly of amphiphilic GC–NABP, which was synthesized by grafting the hydrophobic, H2O2-responsive and two-photon fluorophore, NABP, onto hydrophilic biopolymer glycol chitosan (GC). Taking advantage of pH-titratable amino groups on GC, the nanoprobe had the capability of surface charge conversion from negative at physiologic pH to positive in the acidic tumor microenvironment. The positive charge of the nanoprobe promoted electrostatic interactions with cell membranes, leading to enhanced cellular uptake in acidic environment. Upon cellular uptake, the high level of H2O2 in tumor cells triggered boronate deprotections of the nanoprobe, generating a “turn-on” fluorescence emission for H2O2 imaging. The nanoprobe exhibited good sensitivity and selectivity to H2O2 with a detection limit down to 110 nM in vitro. The results from flow cytometry and two-photon fluorescence imaging of H2O2 in living cells and tissues evidenced the enhanced cellular uptake and targeted imaging of intracellular H2O2 in acidic environment. Compared to control nanoparticles that lack pH sensitivity, our nanoprobe showed enhanced accumulation in tumor sites and was applied to targeted imaging of H2O2 in a tumor-bearing mouse model. This work demonstrates that the nanoprobe GC–NABP holds great promise for tumor-specific imaging of cellular H2O2, providing a potential tool to explore the role of H2O2 in tumor sites.

Graphical abstract: Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide

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Publication details

The article was received on 31 Jul 2019, accepted on 13 Aug 2019 and first published on 20 Aug 2019


Article type: Edge Article
DOI: 10.1039/C9SC03781K
Chem. Sci., 2019,10, 9351-9357
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Tumor-acidity activated surface charge conversion of two-photon fluorescent nanoprobe for enhanced cellular uptake and targeted imaging of intracellular hydrogen peroxide

    L. Chen, S. Xu, W. Li, T. Ren, L. Yuan, S. Zhang and X. Zhang, Chem. Sci., 2019, 10, 9351
    DOI: 10.1039/C9SC03781K

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

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