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. 2022 Nov 22;16(4):5226–5236. doi: 10.1007/s12274-022-5139-z

Reductive damage induced autophagy inhibition for tumor therapy

Yuqian Wang 1,2,3,#, Yingjian Huang 3,#, Yu Fu 4, Zhixiong Guo 2, Da Chen 2, Fangxian Cao 2, Qi Ye 5, Qiqi Duan 3, Meng Liu 3, Ning Wang 3, Dan Han 1, Chaoyi Qu 6, Zhimin Tian 2,✉, Yongquan Qu 2,✉, Yan Zheng 1,✉
PMCID: PMC9684861  PMID: 36465522

Abstract

Numerous therapeutic anti-tumor strategies have been developed in recent decades. However, their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors. Autophagy plays a key role in tumorigenesis and tumor treatment, in which the overproduction of reactive oxygen species (ROS) is recognized as the direct cause of protective autophagy. Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy. Among them, hydroxychloroquine is the most commonly used autophagy inhibitor in clinics, but it is severely limited by its high therapeutic dose, significant toxicity, poor reversal efficacy, and nonspecific action. Herein, we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria (PN-CeO2) nanozymes as autophagy inhibitor. The antineoplastic effects of PN-CeO2 were mediated by its high reductive activity for intratumoral ROS degradation, thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma. Further investigation highlighted PN-CeO2 as a safe and efficient anti-tumor autophagy inhibitor. Overall, this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases.

graphic file with name 12274_2022_5139_Fig1_HTML.jpg

Electronic Supplementary Material

Supplementary material (cellular uptake of PN-CeO2, effects of PN-CeO2 on several common malignant tumor models, viability of HaCaT cells treated with PN-CeO2 at different concentrations, time-dependent body-weight curves of SCL-1 tumor-bearing nude mice, the biodistribution of Ce element in main tissues and tumors after injection of PN-CeO2, measurement of Ce element concentration in urine and feces samples, H&E-stained images of main organs, and measurement of liver and kidney function in mice after different treatment) is available in the online version of this article at 10.1007/s12274-022-5139-z.

Keywords: CeO2, reductive damage, autophagy inhibitor, tumor therapy, reactive oxygen species

Electronic Supplementary Material

12274_2022_5139_MOESM1_ESM.pdf (1.1MB, pdf)

Reductive damage induced autophagy inhibition for tumor therapy

Acknowledgements

We thank Professor Yi Lv and his colleague from the National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research. This work was supported by grants from the National Natural Science Foundation of China (Nos. 81972938, 52002314, and 21872109) and partially supported by Funds of Shaanxi Province (Nos. 2021ZDLSF03-01, 2020TD-043, and TZ0124), General Project of Shaanxi Natural Science Basic Research Plan (No. 2021JM-589), and Xi’an People’s Hospital (Xi’an Fourth Hospital) Research Incubation Fund Project (LH-1). The authors also acknowledge the support from the Fundamental Research Funds for the Central Universities (Nos. D5000210829 and G2021KY05102).

Footnotes

Yuqian Wang and Yingjian Huang contributed equally to this work.

Contributor Information

Zhimin Tian, Email: zhimintian@nwpu.edu.cn.

Yongquan Qu, Email: yongquan@nwpu.edu.cn.

Yan Zheng, Email: zhengyan2018@xjtu.edu.cn.

References

  • [1].Helleday T. Poisoning cancer cells with oxidized nucleosides. N. Engl. J. Med. 2015;373:1570–1571. doi: 10.1056/NEJMcibr1510335. [DOI] [PubMed] [Google Scholar]
  • [2].Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A. ROS in cancer therapy: The bright side of the moon. Exp. Mol. Med. 2020;52:192–203. doi: 10.1038/s12276-020-0384-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic. Biol. Med. 2017;104:144–164. doi: 10.1016/j.freeradbiomed.2017.01.004. [DOI] [PubMed] [Google Scholar]
  • [4].Yang H T, Villani R M, Wang H L, Simpson M J, Roberts M S, Tang M, Liang X W. The role of cellular reactive oxygen species in cancer chemotherapy. J. Exp. Clin. Cancer Res. 2018;37:266. doi: 10.1186/s13046-018-0909-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].Liu C, Lin Q, Yun Z. Cellular and molecular mechanisms underlying oxygen-dependent radiosensitivity. Radiat. Res. 2015;183:487–496. doi: 10.1667/RR13959.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Pham T C, Nguyen V N, Choi Y, Lee S, Yoon J. Recent strategies to develop innovative photosensitizers for enhanced photodynamic therapy. Chem. Rev. 2021;121:13454–13619. doi: 10.1021/acs.chemrev.1c00381. [DOI] [PubMed] [Google Scholar]
  • [7].He G L, Xu N, Ge H Y, Lu Y, Wang R, Wang H X, Du J J, Fan J L, Sun W, Peng X J. Red-light-responsive Ru complex photosensitizer for lysosome localization photodynamic therapy. ACS Appl. Mater. Interfaces. 2021;13:19572–19580. doi: 10.1021/acsami.0c22551. [DOI] [PubMed] [Google Scholar]
  • [8].Yang B W, Chen Y, Shi J L. Reactive oxygen species (ROS)-based nanomedicine. Chem. Rev. 2019;119:4881–4985. doi: 10.1021/acs.chemrev.8b00626. [DOI] [PubMed] [Google Scholar]
  • [9].Chen J J, Zhu Y F, Wu C T, Shi J L. Nanoplatform-based cascade engineering for cancer therapy. Chem. Soc. Rev. 2020;49:9057–9094. doi: 10.1039/D0CS00607F. [DOI] [PubMed] [Google Scholar]
  • [10].Canaparo R, Foglietta F, Limongi T, Serpe L. Biomedical applications of reactive oxygen species generation by metal nanoparticles. Materials (Basel) 2021;14:53. doi: 10.3390/ma14010053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Wang X W, Zhong X Y, Liu Z, Cheng L. Recent progress of chemodynamic therapy-induced combination cancer therapy. Nano Today. 2020;35:100946. doi: 10.1016/j.nantod.2020.100946. [DOI] [Google Scholar]
  • [12].He Y X, Liu S H, Yin J, Yoon J. Sonodynamic and chemodynamic therapy based on organic/organometallic sensitizers. Coord. Chem. Rev. 2021;429:213610. doi: 10.1016/j.ccr.2020.213610. [DOI] [Google Scholar]
  • [13].Zhang C Y, Wang X, Du J F, Gu Z J, Zhao Y L. Reactive oxygen species-regulating strategies based on nanomaterials for disease treatment. Adv. Sci. 2021;8:2002797. doi: 10.1002/advs.202002797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Wang X Q, Wang W J, Peng M Y, Zhang X Z. Free radicals for cancer theranostics. Biomaterials. 2021;266:120474. doi: 10.1016/j.biomaterials.2020.120474. [DOI] [PubMed] [Google Scholar]
  • [15].Fan W P, Yung B, Huang P, Chen X Y. Nanotechnology for multimodal synergistic cancer therapy. Chem. Rev. 2017;117:13566–13638. doi: 10.1021/acs.chemrev.7b00258. [DOI] [PubMed] [Google Scholar]
  • [16].Yang J Y, Zhao Y, Zhou Y Y, Wei X L, Wang H J, Si N, Yang J, Zhao Q H, Bian B L, Zhao H Y. Advanced nanomedicines for the regulation of cancer metabolism. Biomaterials. 2022;286:121565. doi: 10.1016/j.biomaterials.2022.121565. [DOI] [PubMed] [Google Scholar]
  • [17].Wang M, Chang M Y, Li C X, Chen Q, Hou Z Y, Xing B G, Lin J. Tumor-microenvironment-activated reactive oxygen species amplifier for enzymatic cascade cancer starvation/chemodynamic/immunotherapy. Adv. Mater. 2022;34:2106010. doi: 10.1002/adma.202106010. [DOI] [PubMed] [Google Scholar]
  • [18].Zhang X H, Guo R C, Chen Y F, Xu X, Yang Z X, Cheng D B, Chen H, Qiao Z Y, Wang H. A BiOCl nanodevice for pancreatic tumor imaging and mitochondria-targeted therapy. Nano Today. 2021;40:101285. doi: 10.1016/j.nantod.2021.101285. [DOI] [Google Scholar]
  • [19].Filomeni G, De Zio D, Cecconi F. Oxidative stress and autophagy: The clash between damage and metabolic needs. Cell. Death. Differ. 2015;22:377–388. doi: 10.1038/cdd.2014.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Xia H J, Green D R, Zou W P. Autophagy in tumour immunity and therapy. Nat. Rev. Cancer. 2021;21:281–297. doi: 10.1038/s41568-021-00344-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Doherty J, Baehrecke E H. Life, death and autophagy. Nat. Cell Biol. 2018;20:1110–1117. doi: 10.1038/s41556-018-0201-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Huang J, Brumell J H. Bacteria-autophagy interplay: A battle for survival. Nat. Rev. Microbiol. 2014;12:101–114. doi: 10.1038/nrmicro3160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Galluzzi L, Green D R. Autophagy-independent functions of the autophagy machinery. Cell. 2019;177:1682–1699. doi: 10.1016/j.cell.2019.05.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Stukalov A, Girault V, Grass V, Karayel O, Bergant V, Urban C, Haas D A, Huang Y Q, Oubraham L, Wang A Q, et al. Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021;594:246–252. doi: 10.1038/s41586-021-03493-4. [DOI] [PubMed] [Google Scholar]
  • [25].Yamazaki T, Pedro J M B S, Galluzzi L, Kroemer G, Pietrocola F. Autophagy in the cancer-immunity dialogue. Adv. Drug Deliv. Rev. 2021;169:40–50. doi: 10.1016/j.addr.2020.12.003. [DOI] [PubMed] [Google Scholar]
  • [26].Wang L, Wang Y T, Zhao W, Lin K L, Li W, Wang G D, Zhang Q. Library screening to identify highly-effective autophagy inhibitors for improving photothermal cancer therapy. Nano Lett. 2021;21:9476–9484. doi: 10.1021/acs.nanolett.1c02825. [DOI] [PubMed] [Google Scholar]
  • [27].Gao G, Sun X B, Liu X Y, Jiang Y W, Tang R Q, Guo Y X, Wu F G, Liang G L. Intracellular nanoparticle formation and hydroxychloroquine release for autophagy-inhibited mild-temperature photothermal therapy for tumors. Adv. Funct. Mater. 2021;31:2102832. doi: 10.1002/adfm.202102832. [DOI] [Google Scholar]
  • [28].Wang X H, Li M, Ren K B, Xia C Y, Li J P, Yu Q W, Qiu Y, Lu Z Z, Long Y, Zhang Z R, et al. On-demand autophagy cascade amplification nanoparticles precisely enhanced oxaliplatin-induced cancer immunotherapy. Adv. Mater. 2020;32:2002160. doi: 10.1002/adma.202002160. [DOI] [PubMed] [Google Scholar]
  • [29].Xie Y X, Jiang J N, Tang Q Y, Zou H B, Zhao X, Liu H M, Ma D, Cai C L, Zhou Y, Chen X J, et al. Iron oxide nanoparticles as autophagy intervention agents suppress hepatoma growth by enhancing tumoricidal autophagy. Adv. Sci. 2020;7:1903323. doi: 10.1002/advs.201903323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Shashni B, Nagasaki Y. Nitroxide radical-containing nanoparticles attenuate tumorigenic potential of triple negative breast cancer. Biomaterials. 2018;178:48–62. doi: 10.1016/j.biomaterials.2018.05.042. [DOI] [PubMed] [Google Scholar]
  • [31].Wang J F, Zhou X F, Wang H F, Xiao Q, Ding K F, Dong X, Xu S F, Shen B, Sun J H, Zhou Z X, et al. Autophagy-inhibiting polymer as an effective nonviral cancer gene therapy vector with inherent apoptosis-sensitizing ability. Biomaterials. 2020;255:120156. doi: 10.1016/j.biomaterials.2020.120156. [DOI] [PubMed] [Google Scholar]
  • [32].Kim K Y, Park K I, Kim S H, Yu S N, Park S G, Kim Y W, Seo Y K, Ma J Y, Ahn S C. Inhibition of autophagy promotes salinomycin-induced apoptosis via reactive oxygen species-mediated PI3K/AKT/mTOR and ERK/p38 MAPK-dependent signaling in human prostate cancer cells. Int. J. Mol. Sci. 2017;18:1088. doi: 10.3390/ijms18051088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Xu J, Wang H S, Hu Y, Zhang Y S, Wen L P, Yin F, Wang Z Y, Zhang Y C, Li S Y, Miao Y Y, et al. Inhibition of CaMKIIα activity enhances antitumor effect of fullerene C60 nanocrystals by suppression of autophagic degradation. Adv. Sci. 2019;6:1801233. doi: 10.1002/advs.201801233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Wei W J, Rosenkrans Z T, Luo Q Y, Lan X L, Cai W B. Exploiting nanomaterial-mediated autophagy for cancer therapy. Small Methods. 2019;3:1800365. doi: 10.1002/smtd.201800365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Chen M L, Yang D, Sun Y, Liu T, Wang W H, Fu J T, Wang Q Q, Bai X Q, Quan G L, Pan X, et al. In situ self-assembly nanomicelle microneedles for enhanced photoimmunotherapy via autophagy regulation strategy. ACS Nano. 2021;15:3387–3401. doi: 10.1021/acsnano.0c10396. [DOI] [PubMed] [Google Scholar]
  • [36].Li F L, Chen T, Wang F, Chen J F, Zhang Y Y, Song D T, Li N, Lin X H, Lin L S, Zhuang J Y. Enhanced cancer starvation therapy enabled by an autophagy inhibitors-encapsulated biomimetic ZIF-8 nanodrug: Disrupting and harnessing dual pro-survival autophagic responses. ACS Appl. Mater. Interfaces. 2022;14:21860–21871. doi: 10.1021/acsami.2c00552. [DOI] [PubMed] [Google Scholar]
  • [37].Wang M, Chen Q, Xu D, Yang Z B, Chen J F, Zhang Y, Chen H R. Self-cycling redox nanoplatform in synergy with mild magnetothermal and autophagy inhibition for efficient cancer therapy. Nano Today. 2022;43:101374. doi: 10.1016/j.nantod.2022.101374. [DOI] [Google Scholar]
  • [38].Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: Implications for rheumatology. Nat. Rev. Rheumatol. 2020;16:155–166. doi: 10.1038/s41584-020-0372-x. [DOI] [PubMed] [Google Scholar]
  • [39].Ruan S B, Xie R, Qin L, Yu M N, Xiao W, Hu C, Yu W Q, Qian Z Y, Ouyang L, He Q, et al. Aggregable nanoparticles-enabled chemotherapy and autophagy inhibition combined with anti-PD-L1 antibody for improved glioma treatment. Nano Lett. 2019;19:8318–8332. doi: 10.1021/acs.nanolett.9b03968. [DOI] [PubMed] [Google Scholar]
  • [40].Shen W T, Zhang X Y, Fu X, Fan J J, Luan J Y, Cao Z L, Yang P, Xu Z Y, Ju D W. A novel and promising therapeutic approach for NSCLC: Recombinant human arginase alone or combined with autophagy inhibitor. Cell Death Dis. 2017;8:e2720. doi: 10.1038/cddis.2017.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Bellare G P, Patro B S. Resveratrol sensitizes breast cancer to PARP inhibitor, talazoparib through dual inhibition of AKT and autophagy flux. Biochem. Pharmacol. 2022;199:115024. doi: 10.1016/j.bcp.2022.115024. [DOI] [PubMed] [Google Scholar]
  • [42].Wang Q, Cheng C Q, Zhao S, Liu Q Y, Zhang Y H, Liu W L, Zhao X Z, Zhang H, Pu J, Zhang S, et al. A valence-engineered self-cascading antioxidant nanozyme for the therapy of inflammatory bowel disease. Angew. Chem., Int. Ed. 2022;61:e202201101. doi: 10.1002/anie.202201101. [DOI] [PubMed] [Google Scholar]
  • [43].Wang L Y, Zhu B H, Deng Y T, Li T T, Tian Q Y, Yuan Z G, Ma L, Cheng C, Guo Q Y, Qiu L. Biocatalytic and antioxidant nanostructures for ROS scavenging and biotherapeutics. Adv. Funct. Mater. 2021;31:2101804. doi: 10.1002/adfm.202101804. [DOI] [Google Scholar]
  • [44].Wu J J, Wang X Y, Wang Q, Lou Z P, Li S R, Zhu Y Y, Qin L, Wei H. Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes(II) Chem. Soc. Rev. 2019;48:1004–1076. doi: 10.1039/C8CS00457A. [DOI] [PubMed] [Google Scholar]
  • [45].Wang H, Wan K W, Shi X H. Recent advances in nanozyme research. Adv. Mater. 2019;31:1805368. doi: 10.1002/adma.201805368. [DOI] [PubMed] [Google Scholar]
  • [46].Huang Y Y, Ren J S, Qu X G. Nanozymes: Classification, catalytic mechanisms, activity regulation, and applications. Chem. Rev. 2019;119:4357–4412. doi: 10.1021/acs.chemrev.8b00672. [DOI] [PubMed] [Google Scholar]
  • [47].Jiang D W, Ni D L, Rosenkrans Z T, Huang P, Yan X Y, Cai W B. Nanozyme: New horizons for responsive biomedical applications. Chem. Soc. Rev. 2019;48:3683–3704. doi: 10.1039/C8CS00718G. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Tang G H, He J Y, Liu J W, Yan X Y, Fan K L. Nanozyme for tumor therapy: Surface modification matters. Exploration. 2021;1:75–89. doi: 10.1002/EXP.20210005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [49].Zhao S, Li Y X, Liu Q Y, Li S R, Cheng Y, Cheng C Q, Sun Z Y, Du Y, Butch C J, Wei H. An orally administered CeO2@montmorillonite nanozyme targets inflammation for inflammatory bowel disease therapy. Adv. Funct. Mater. 2020;30:2004692. doi: 10.1002/adfm.202004692. [DOI] [Google Scholar]
  • [50].Tian Z M, Li X H, Ma Y Y, Chen T, Xu D H, Wang B C, Qu Y Q, Gao Y. Quantitatively intrinsic biomimetic catalytic activity of nanocerias as radical scavengers and their ability against H2O2 and doxorubicin-induced oxidative stress. ACS Appl. Mater. Interfaces. 2017;9:23342–23352. doi: 10.1021/acsami.7b04761. [DOI] [PubMed] [Google Scholar]
  • [51].Weng Q J, Sun H, Fang C Y, Xia F, Liao H W, Lee J, Wang J C, Xie A, Ren J F, Guo X, et al. Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics. Nat. Commun. 2021;12:1436. doi: 10.1038/s41467-021-21714-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [52].Tian Z M, Zhao J L, Zhao S J, Li H C, Guo Z X, Liang Z C, Li J Y, Qu Y Q, Chen D F, Liu L. Phytic acid-modified CeO2 as Ca2+ inhibitor for a security reversal of tumor drug resistance. Nano Res. 2022;15:4334–4343. doi: 10.1007/s12274-022-4069-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [53].Naha P C, Hsu J C, Kim J, Shah S, Bouché M, Si-Mohamed S, Rosario-Berrios D N, Douek P, Hajfathalian M, Yasini P, et al. Dextran-coated cerium oxide nanoparticles: A computed tomography contrast agent for imaging the gastrointestinal tract and inflammatory bowel disease. ACS Nano. 2020;14:10187–10197. doi: 10.1021/acsnano.0c03457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [54].Soh M, Kang D W, Jeong H G, Kim D, Kim D Y, Yang W, Song C, Baik S, Choi I Y, Ki S K, et al. Ceria-zirconia nanoparticles as an enhanced multi-antioxidant for sepsis treatment. Angew. Chem., Int. Ed. 2017;56:11399–11403. doi: 10.1002/anie.201704904. [DOI] [PubMed] [Google Scholar]
  • [55].Karakoti A, Singh S, Dowding J M, Seal S, Self W T. Redox-active radical scavenging nanomaterials. Chem. Soc. Rev. 2010;39:4422–4432. doi: 10.1039/b919677n. [DOI] [PubMed] [Google Scholar]
  • [56].Boey A, Leong S Q, Bhave S, Ho H K. Cerium oxide nanoparticles alleviate hepatic fibrosis phenotypes in vitro. Int. J. Mol. Sci. 2021;22:11777. doi: 10.3390/ijms222111777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [57].Global Burden of Disease 2019 Cancer Collaboration Disease 2019 Cancer Collaboration. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: A systematic analysis for the global burden of disease study 2019. JAMA Oncol. 2022;8:420–444. doi: 10.1001/jamaoncol.2021.6987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [58].White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat. Rev. Cancer. 2012;12:401–410. doi: 10.1038/nrc3262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [59].Chae Y C, Vaira V, Caino M C, Tang H Y, Seo J H, Kossenkov A V, Ottobrini L, Martelli C, Lucignani G, Bertolini I, et al. Mitochondrial Akt regulation of hypoxic tumor reprogramming. Cancer Cell. 2016;30:257–272. doi: 10.1016/j.ccell.2016.07.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [60].Mirshafiee V, Sun B B, Chang C H, Liao Y P, Jiang W, Jiang J H, Liu X S, Wang X, Xia T, Nel A E. Toxicological profiling of metal oxide nanoparticles in liver context reveals pyroptosis in Kupffer cells and macrophages versus apoptosis in hepatocytes. ACS Nano. 2018;12:3836–3852. doi: 10.1021/acsnano.8b01086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [61].Levine B, Kroemer G. Biological functions of autophagy genes: A disease perspective. Cell. 2019;176:11–42. doi: 10.1016/j.cell.2018.09.048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [62].Moscat J, Karin M, Diaz-Meco M T. p62 in cancer: Signaling adaptor beyond autophagy. Cell. 2016;167:606–609. doi: 10.1016/j.cell.2016.09.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [63].Yang B W, Ding L, Yao H L, Chen Y, Shi J L. A metal-organic framework (MOF) Fenton nanoagent-enabled nanocatalytic cancer therapy in synergy with autophagy inhibition. Adv. Mater. 2020;32:1907152. doi: 10.1002/adma.201907152. [DOI] [PubMed] [Google Scholar]
  • [64].Jang J, Wang Y D, Lalli M A, Guzman E, Godshalk S E, Zhou H J, Kosik K S. Primary cilium-autophagy-Nrf2 (PAN) axis activation commits human embryonic stem cells to a neuroectoderm fate. Cell. 2016;165:410–420. doi: 10.1016/j.cell.2016.02.014. [DOI] [PubMed] [Google Scholar]
  • [65].Tai W Y, Li J W, Corey E, Gao X H. A ribonucleoprotein octamer for targeted siRNA delivery. Nat. Biomed. Eng. 2018;2:326–337. doi: 10.1038/s41551-018-0214-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [66].Chen L J, Jiang X W, Lv M, Wang X L, Zhao P R, Zhang M, Lv G L, Wu J Y, Liu Y Y, Yang Y, et al. Reductive-damage-induced intracellular maladaptation for cancer electronic interference therapy. Chem. 2022;8:866–879. doi: 10.1016/j.chempr.2022.02.010. [DOI] [Google Scholar]

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12274_2022_5139_MOESM1_ESM.pdf (1.1MB, pdf)

Reductive damage induced autophagy inhibition for tumor therapy

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