Journal Home > Volume 16 , Issue 4
Nano Research 2023, 16(4): 5226-5236 https://doi.org/10.1007/s12274-022-5139-z
Research Article | Issue | Published: 22 November 2022

Reductive damage induced autophagy inhibition for tumor therapy

Show Author's Information Yuqian Wang1,2,3,§,  Yingjian Huang3,§,  Yu Fu4,  Zhixiong Guo2,  Da Chen2,  Fangxian Cao2,  Qi Ye5,  Qiqi Duan3,  Meng Liu3,  Ning Wang3,  Dan Han1,  Chaoyi Qu6,  Zhimin Tian2( ),  Yongquan Qu2( ),  Yan Zheng1( )
Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an 710072, China
Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, China
School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Xi’an Jiaotong University, Xi’an 710049, China
Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, China

§ Yuqian Wang and Yingjian Huang contributed equally to this work.

Keywords:
CeO2, tumor therapy, reactive oxygen species, reductive damage, autophagy inhibitor
Topics:
Nano biology
Cite this article:
Wang Y, Huang Y, Fu Y, et al. Reductive damage induced autophagy inhibition for tumor therapy. Nano Research, 2023, 16(4): 5226-5236. https://doi.org/10.1007/s12274-022-5139-z
Download citation
EndNote(RIS)
BibTeX

758

Views

71

Downloads

Citations

4

Crossref

3

WoS

5

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

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.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Reductive damage induced autophagy inhibition for tumor therapy

Show Author's information Yuqian Wang1,2,3,§, Yingjian Huang3,§, Yu Fu4, Zhixiong Guo2, Da Chen2, Fangxian Cao2, Qi Ye5, Qiqi Duan3, Meng Liu3, Ning Wang3, Dan Han1, Chaoyi Qu6, Zhimin Tian2( ), Yongquan Qu2( ), Yan Zheng1( )
Department of Dermatology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi’an 710072, China
Department of Dermatology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, China
School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Xi’an Jiaotong University, Xi’an 710049, China
Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Xi’an People’s Hospital (Xi’an Fourth Hospital), Shaanxi Eye Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710004, China

§ Yuqian Wang and Yingjian Huang contributed equally to this work.

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.

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

References(66)

[1]

Helleday, T. Poisoning cancer cells with oxidized nucleosides. N. Engl. J. Med. 2015, 373, 1570–1571.
DOI 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 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 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 Google Scholar
[5]

Liu, C.; Lin, Q.; Yun, Z. Cellular and molecular mechanisms underlying oxygen-dependent radiosensitivity. Radiat. Res. 2015, 183, 487–496.
DOI 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 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 Google Scholar
[8]

Yang, B. W.; Chen, Y.; Shi, J. L. Reactive oxygen species (ROS)-based nanomedicine. Chem. Rev. 2019, 119, 4881–4985.
DOI 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 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 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 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 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 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 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 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 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 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 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 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 Google Scholar
[21]

Doherty, J.; Baehrecke, E. H. Life, death and autophagy. Nat. Cell Biol. 2018, 20, 1110–1117.
DOI Google Scholar
[22]

Huang, J.; Brumell, J. H. Bacteria-autophagy interplay: A battle for survival. Nat. Rev. Microbiol. 2014, 12, 101–114.
DOI Google Scholar
[23]

Galluzzi, L.; Green, D. R. Autophagy-independent functions of the autophagy machinery. Cell 2019, 177, 1682–1699.
DOI 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Google Scholar
[45]

Wang, H.; Wan, K. W.; Shi, X. H. Recent advances in nanozyme research. Adv. Mater. 2019, 31, 1805368.
DOI 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 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 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 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 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 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 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 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 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 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 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 Google Scholar
[57]

Global Burden of 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 Google Scholar
[58]

White, E. Deconvoluting the context-dependent role for autophagy in cancer. Nat. Rev. Cancer 2012, 12, 401–410.
DOI 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 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 Google Scholar
[61]

Levine, B.; Kroemer, G. Biological functions of autophagy genes: A disease perspective. Cell 2019, 176, 11–42.
DOI Google Scholar
[62]

Moscat, J.; Karin, M.; Diaz-Meco, M. T. p62 in cancer: Signaling adaptor beyond autophagy. Cell 2016, 167, 606–609.
DOI 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 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 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 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 Google Scholar
File
12274_2022_5139_MOESM1_ESM.pdf (1.1 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 27 July 2022
Revised: 27 September 2022
Accepted: 02 October 2022
Published: 22 November 2022
Issue date: April 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

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).

Return