Kaixuan Yang1,2,3, Ying Lu1, Fangyuan Xie1,4, Hao Zou1, Xiaoyu Fan2, Bohua Li2, Wei Li2, Wei Zhang5, Lin Mei6, Si-Shen Feng2,7, You Yin8, Yan Liu9, Hai Zhang4, Chuan Yin10, Yanqiang Zhong1, Jie Gao1,2,11. 1. Department of Pharmaceutical Sciences, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. 2. International Joint Cancer Institute, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China. 3. Department of Oncology, Affiliated Hospital of Guizhou Medcial University & Guizhou Cancer Hospital, Guiyang 550025, Guizhou, China. 4. Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, 225 Changhai Road, Shanghai 200438, China. 5. Department of Respiratory & Critical Care Medicine, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China. 6. Division of Life & Health Sciences, Tsinghua University Shenzhen Graduate School, Shenzhen 518055, China. 7. Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore. 8. Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. 9. Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. 10. Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. 11. Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
AIM: The application of cationic liposomes (CLs) as nonviral vectors is hampered by their cellular toxicity. Thus we aim to investigate the mechanisms underlying the cellular toxicity of CLs. MATERIALS & METHODS: The effect of CLs on the autophagic flux, autophagosome-lysosome fusion, lysosome membrane permeabilization and cell necrosis of liver cells was investigated. RESULTS & CONCLUSION: Our results reveal a novel mechanism of CL-induced cell necrosis involving the induction of lysosome membrane permeabilization and late-stage autophagic flux inhibition that resulted in cytoplasmic release of cathepsin B, mitochondrial dysfunction and reactive oxygen species production, which are the key mediators of cell necrosis. Our study is important for revealing the cellular toxicity of CLs and designing safer gene delivery systems.
AIM: The application of cationic liposomes (CLs) as nonviral vectors is hampered by their cellular toxicity. Thus we aim to investigate the mechanisms underlying the cellular toxicity of CLs. MATERIALS & METHODS: The effect of CLs on the autophagic flux, autophagosome-lysosome fusion, lysosome membrane permeabilization and cell necrosis of liver cells was investigated. RESULTS & CONCLUSION: Our results reveal a novel mechanism of CL-induced cell necrosis involving the induction of lysosome membrane permeabilization and late-stage autophagic flux inhibition that resulted in cytoplasmic release of cathepsin B, mitochondrial dysfunction and reactive oxygen species production, which are the key mediators of cell necrosis. Our study is important for revealing the cellular toxicity of CLs and designing safer gene delivery systems.
Authors: Olja Mijanović; Ana Branković; Alexander N Panin; Solomiia Savchuk; Peter Timashev; Ilya Ulasov; Maciej S Lesniak Journal: Cancer Lett Date: 2019-02-20 Impact factor: 8.679
Authors: Siyue Zhang; Fangyuan Xie; Kaichun Li; He Zhang; You Yin; Yuan Yu; Guangzhao Lu; Shihao Zhang; Yan Wei; Ke Xu; Yan Wu; Hong Jin; Lan Xiao; Leilei Bao; Can Xu; Yulin Li; Ying Lu; Jie Gao Journal: Acta Pharm Sin B Date: 2022-02-16 Impact factor: 14.903
Authors: Kara M de la Harpe; Pierre P D Kondiah; Yahya E Choonara; Thashree Marimuthu; Lisa C du Toit; Viness Pillay Journal: Cells Date: 2019-10-07 Impact factor: 6.600
Authors: Khaled S Allemailem; Ahmad Almatroudi; Faris Alrumaihi; Saleh A Almatroodi; Mohammad O Alkurbi; Ghaiyda Talal Basfar; Arshad Husain Rahmani; Amjad Ali Khan Journal: Int J Nanomedicine Date: 2021-07-26