Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-canc...Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy.However,the development of ferroptosis-based nanotherapeutics is generally hindered by the limited penetration depth in tumors,poor active pharmaceutical ingredient(API)loading content and the systemic toxicity.Herein,self-propelled ferroptosis nanoinducers composed of two endogenous proteins,glucose oxidase and ferritin,are presented to show enhanced tumor inhibition via ferroptosis while maintaining high API and biocompatibility.The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin.The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H_(2)O_(2),leading to deeper penetration and enhanced uptake into tumors.Under the synergistic effect of glucose oxidase and ferritin,the equilibrium between reactive oxygen species and GSH is damaged,leading to lipid peroxidation.As a result,by inducing ferroptosis,our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibitory effects.This work paves a way for the construction of a biocompatible anticancer platform with enhanced diffusion utilizing only two endogenous proteins,centered around the concept of ferroptosis.展开更多
A potential reason for the failure of tumor therapies is treatment resistance.Resistance to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and meta...A potential reason for the failure of tumor therapies is treatment resistance.Resistance to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and metastasis.The major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,etc.Recent studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell death.Some ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor therapy.Notably,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback regulation.Herein,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor therapeutics.We also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.展开更多
基金supported by National Key Research and Development Program of China(No.2022YFA1206900)National Natural Science Foundation of China(Nos.22175083,82204415,51973241,22375224)GuangDong Basic and Applied Basic Research Foundation(No.2021A1515220187)。
文摘Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy.However,the development of ferroptosis-based nanotherapeutics is generally hindered by the limited penetration depth in tumors,poor active pharmaceutical ingredient(API)loading content and the systemic toxicity.Herein,self-propelled ferroptosis nanoinducers composed of two endogenous proteins,glucose oxidase and ferritin,are presented to show enhanced tumor inhibition via ferroptosis while maintaining high API and biocompatibility.The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin.The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H_(2)O_(2),leading to deeper penetration and enhanced uptake into tumors.Under the synergistic effect of glucose oxidase and ferritin,the equilibrium between reactive oxygen species and GSH is damaged,leading to lipid peroxidation.As a result,by inducing ferroptosis,our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibitory effects.This work paves a way for the construction of a biocompatible anticancer platform with enhanced diffusion utilizing only two endogenous proteins,centered around the concept of ferroptosis.
基金This work was supported by the National Natural Science Foundation of China(81901794)the China Postdoctoral Science Foundation funded project(2021M693632)Guangdong Provincial Fund for Distinguished Young Scholars(2021B1515020066)。
文摘A potential reason for the failure of tumor therapies is treatment resistance.Resistance to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and metastasis.The major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,etc.Recent studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell death.Some ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor therapy.Notably,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback regulation.Herein,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor therapeutics.We also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.
