An iron-based metal-organic framework nanoplatform for enhanced ferroptosis and oridonin delivery as a comprehensive antitumor strategy  

作　　者：Mengru Cai Tingting Fu Rongyue Zhu Panxiang Hu Jiahui Kong Shilang Liao Yuji Du Yongqiang Zhang Changhai Qu Xiaoxv Dong Xingbin Yin Jian Ni 

机构地区：[1]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第9期4073-4086,共14页药学学报（英文版）

基　　金：the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(No.CACM-QNRC2-A03,China);the Beijing Natural Science Foundation(No.7202121,China);the National Natural Science Foundation of China(No.81703715).

摘　　要：Ferroptosis is a recently discovered pathway for regulated cell death pathway.However,its efficacy is affected by limited iron content and intracellular ion homeostasis.Here,we designed a metalorganic framework(MOF)-based nanoplatform that incorporates calcium peroxide(CaO_(2))and oridonin(ORI).This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis,thereby enhancing ferroptosis therapy.Fused cell membranes(FM)were used to modify nanoparticles(ORI@CaO_(2)@Fe-TCPP,NPs)to produce FM@ORI@CaO_(2)@Fe-TCPP(FM@NPs).The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously,working in tandem with Fe^(3+) to induce ferroptosis.Photodynamic therapy(PDT)guided by porphyrin(TCPP)significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species(ROS).This selfamplifying strategy promoted robust ferroptosis,which could work synergistically with FM-mediated immunotherapy.In vivo experiments showed that FM@NPs inhibited 91.57%of melanoma cells within six days,a rate 5.6 times higher than chemotherapy alone.FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity.Thus,this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.

关 键 词：Metal-organic frameworks IMMUNOTHERAPY Self-amplifying ferroptosis Photodynamic therapy Chemodynamic therapy ORIDONIN Fused cell membrane coating Metabolization 

分 类 号：R318[医药卫生—生物医学工程]