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Cerium oxide nanoparticles-mediated cascade catalytic chemo-photo tumor combination therapy

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Abstract

ROS-based tumor therapy based on nanocatalytic medicine has recently been proposed for its tumor-specificity. However, a safe and highly efficient strategy towards getting high enough ROS to kill the hypoxic cancer cells is still a great challenge. Herein, we report a simple pH/H2O2-activatable, O2-evolving, and ROS regulating doxorubicin (DOX) and indocyanine green (ICG) co-loading PEGylated polyaniline (PANI) coated CeOx@polyacrylic acid (PAA) nanoclusters for highly selective and optimized cancer combination treatment. It can selectively and greatly enhance intracellular O2 and ROS levels in tumor region, which depends on two-step catalytic properties of nanoceria (Ce4+/Ce3+ = 3.46, neutral surface charge, mostly localize into the cytoplasm, pH 7.4–6.5, catalase-like catalytic agents convert to Ce4+/Ce3+ = 0.58, negative surface charge, mostly localize into the lysosomes, pH 5–4, oxidase-like catalytic agents, triggered by near infrared (NIR) laser irradiation). Furthermore, the protective effect of polyethylene glycol (PEG), PANI, and PAA ensure that the nanoceria can only play the role of catalase under the irradiation of NIR light arrived at the tumor area. Moreover, loading of nanoceria and ICG onto PANI greatly enhanced photo thermal effect of nanoparticles (NPs), which is useful for killing cancer cells by relieving hypoxia and promoting cross-membrane drug delivery to further enhance photodynamic therapy and chemotherapy efficiency. The chemo-photo combination therapies fantastically inhibited tumor growth and prevented tumor recurrence in vivo, suggesting a smart nanotheranostic system to achieve more precise and effective therapies in O2-deprived tumor tissue.

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Acknowledgements

This work was supported by The National Key Research and Development Program of China (Nos. 2018YFF0215500), National Natural Science Foundation of China (Nos. 21105047, 51773089, and 51973091), the Natural Science Foundation of Jiangsu Province (Nos. BK20181204 and BK20171258), and the Science and Technology Items Fund of Nantong City (Applied Basic Research Programs 2017-N, No. MS12017027-2).

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  1. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China

    Zitao Hu & Yin Ding

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Correspondence to Yin Ding.

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Hu, Z., Ding, Y. Cerium oxide nanoparticles-mediated cascade catalytic chemo-photo tumor combination therapy. Nano Res. 15, 333–345 (2022). https://doi.org/10.1007/s12274-021-3480-2

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