Abstract
Dynamic therapies have potential in cancer treatments but have limitations in efficiency and penetration depth. Here a membrane-integrated liposome (MIL) is created to coat titanium dioxide (TiO2) nanoparticles to enhance electron transfer and increase radical production under low-dose X-ray irradiation. The exoelectrogenic Shewanella oneidensis MR-1 microorganism presents an innate capability for extracellular electron transfer (EET). An EET-mimicking photocatalytic system is created by coating the TiO2 nanoparticles with the MIL, which significantly enhances superoxide anions generation under low-dose (1 Gy) X-ray activation. The c-type cytochromes-constructed electron channel in the membrane mimics electron transfer to surrounding oxygen. Moreover, the hole transport in the valence band is also observed for water oxidation to produce hydroxyl radicals. The TiO2@MIL system is demonstrated against orthotopic liver tumours in vivo.
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Data availability
The data that support the findings of this study are available from the corresponding authors upon reasonable request. Source data are provided with this paper.
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Acknowledgements
C.-S.Y. appreciates the financial support provided by National Science and Technology Council, Taiwan (109-2113-M-006 -011-MY3). This research was also supported in part by Higher Education Sprout Project, Ministry of Education to the Headquarters of University Advancement at National Cheng Kung University. Additional financially support was provided by the Center of Applied Nanomedicine, National Cheng Kung University under the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project of the Ministry of Education (MOE) in Taiwan. W.-P.L. appreciates the financial support by the National Science and Technology Council, Taiwan (NSTC 109-2113-M-037-017-MY3 and NSTC 111-2320-B-037-035), Kaohsiung Medical University Research Foundation (KMU-Q111002) and the Yushan Young Scholar Program of the Ministry of Education of Taiwan. C.-H.S. thanks the financial support by the National Science and Technology Council, Taiwan (NSTC 109-2314-B-182-011-MY3; 111-2811-B-182-033-) and the Chang Gung Medical Foundation (CMRPG8M1021-3 and CMRPG8M0121-3). This work was also supported by a Grant-in-Aid for Research from the Japan Society for Promotion of Science KAKENHI (grant number 22H02265); PRIME, the Japan Agency for Medical Research and Development (grant number 19gm6010002h0004); and JST, PRESTO (grant number JPMJPR19H1). We thank the equipment support provided by the Core Research Laboratory, College of Medicine, National Cheng Kung University, and the Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, National Science and Technology Council, Taiwan. We also thank W.-T. Chiu for his constructive comments on this work.
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C.-S.Y. conceived the research. W.-P.L., C.-H.S., A.O. and C.-S.Y. designed the experiments and supervised the whole project. Y.-C.C., Y.-T.L. and Y.-T.K. synthesized and characterized the TiO2 NPs. W.-P.L., X.L. and A.O. provided the LIME technique and all bacteria. Y.-C.C., Y.-T.L., C.-L.H., M.-C.H, X.L., J.-S.C. and Y.-T.K. fabricated the liposomes and MILs. C.-L.H., M.-C.H. and X.L. contributed to the protein characterization analysis. W.-P.L., A.O. and C.-S.Y. carried out the mechanism analysis. Y.-C.C. and Y.-T.L. performed experiments in the evaluation of ROS generation and in vitro studies. C.-H.S. designed the experiments of animal disease model. C.-L.L., W.-C.L. and C.-H.S. helped with experiments in colony assay and in vivo studies. Y.-C.C., W.-P.L., C.-H.S., A.O. and C.-S.Y. wrote the paper. All the authors have discussed the experimental data, reviewed the paper and commented on the paper.
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Chen, YC., Li, YT., Lee, CL. et al. Electroactive membrane fusion-liposome for increased electron transfer to enhance radiodynamic therapy. Nat. Nanotechnol. 18, 1492–1501 (2023). https://doi.org/10.1038/s41565-023-01476-2
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DOI: https://doi.org/10.1038/s41565-023-01476-2