Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn2(CO)10) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H2O2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO2 and Ce6 to produce center dot OH and 1O2, respectively. The further cascade reaction between ROS and Mn2(CO)10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers.
基金:
National Natural Science Foundation of China; National Key R&D Program of China [2023YFC2508604, 2023YFC2508600]; Excellent Young Science Fund for National Natural Science Foundation of China [82022033]; Shanghai Shenkang Hospital Development Center [SHDC2022CRD048]; Science and Technology Commission of Shanghai Municipality [22XD1402500]; Fundamental Research Funds for the Central Universities [22120210561]; [82072568]; [82373320]
第一作者机构:[1]Tongji Univ, Med Sch, Canc Inst, Dept Med Oncol,Shanghai Pulm Hosp, Shanghai 200092, Peoples R China
通讯作者:
通讯机构:[2]Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Cent Lab, 301 Yan Chang Zhong Rd, Shanghai 200072, Peoples R China[3]Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Orthopaed, 301 Yan Chang Zhong Rd, Shanghai 200072, Peoples R China[4]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Cent Lab, Sichuan Acad Med Sci, 32,West Second Sect,First Ring Rd, Chengdu 610072, Sichuan, Peoples R China
推荐引用方式(GB/T 7714):
Fang Yujia,Yang Jianjun,Liang Xiayi,et al.Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against lung cancer[J].JOURNAL OF NANOBIOTECHNOLOGY.2024,22(1):doi:10.1186/s12951-024-02688-x.
APA:
Fang, Yujia,Yang, Jianjun,Liang, Xiayi,Wu, Jing,Xie, Mengqing...&Su, Chunxia.(2024).Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against lung cancer.JOURNAL OF NANOBIOTECHNOLOGY,22,(1)
MLA:
Fang, Yujia,et al."Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against lung cancer".JOURNAL OF NANOBIOTECHNOLOGY 22..1(2024)