Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis  

作　　者：Chengcheng Wang JiaoWang Xue Pan Shuang Yu Meiqi Chen Yan Gao Zilin Song Haiyang Hu Xiuli Zhao Dawei Chen Fei Han Mingxi Qiao 

机构地区：[1]School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Yantai Luyin Pharmaceutical Co.Ltd.,Yantai 264002,China [3]Qingdao Marine Biomedical Research Institute,Qingdao 266071,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2023年第1期86-96,共11页亚洲药物制剂科学（英文）

摘　　要：As a non-apoptotic cell death form,ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance.However,accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms.To address this issue,we prepared a Buthionine-(S,R)-sulfoximine(BSO)loaded metal organic framework(MOF)of BSO-MOF-HA(BMH)with the combination effect of boosting oxidative damage and inhibiting antioxidative defense.MOF nanoparticle was constructed by the photosensitizer of[4,4,4,4-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid)](TCPP)and the metal ion of Zr6,which was further decorated with hyaluronic acid(HA)in order to impart active targeting to CD44 receptors overexpressed cancer cells.BMH exhibited a negative charge and spherical shape with average particle size about 162.5nm.BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation.This was attributed to the combination of photodynamic therapy(PDT)andγ-glutamylcysteine synthetase inhibitor of BSO,shifting the redox balance to oxidative stress.Enhanced ferroptosis also induced the release of damage associated molecular patterns(DAMPs)to maturate dendritic cells and activated T lymphocytes,leading to superior anti-tumor performance in vivo.Taken together,our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.

关 键 词：Ferroptosis Buthionine-(S R)-sulfoximine GLUTATHIONE Metal organic framework Photodynamic therapy Immunogenic cell death 

分 类 号：R730.53[医药卫生—肿瘤]