Phototherapy, including photodynamic therapy(PDT) and photothermal therapy (PTT), is a promisingmethod of tumor treatment, which has the advantages ofstrong specificity and small side effects. However, PDT willaggrava...Phototherapy, including photodynamic therapy(PDT) and photothermal therapy (PTT), is a promisingmethod of tumor treatment, which has the advantages ofstrong specificity and small side effects. However, PDT willaggravate the hypoxic environment in tumor cells, and PTTwill lead to heat-resistant reaction, both of which will make theorganism quickly produce heat shock proteins (HSPs) toprotect itself, thus seriously hindering the therapeuticefficiency of phototherapy. As a natural HSPs inhibitor,quercetin (QR) provides a feasible way to solve this problem.Herein, a kind of metal organic framework (MOF), Fe-TCPP(FT), was used as a delivery material and photosensitizer tobuild a chemo-phototherapy platform, and QR was used as achemotherapy drug and HSPs inhibitor. On this basis, the nanoparticles (NPs) were modified with PEG-CPP30 (a cellpenetratingpeptide that specifically recognizes human breast cancer MCF-7 cells), which showed excellent targetingcapacity and biocompatibility. The combination of chemotherapy and phototherapy significantly improved the anti-cancereffect. At the same time, NPs also showed prominent anti-HSPs effect. The effective connection of the two played acomplementary role in the process of tumor treatment, which provided a new strategy for the accurate and efficienttreatment of tumors in the future.展开更多
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)-b...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.展开更多
基金funded by Young Elite Scientists Sponsorship Program by CACM(No.2021-QNRC2-A03)the Beijing Natural Science Foundation(No.7202121)the National Natural Science Foundation of China(No.81703715).
文摘Phototherapy, including photodynamic therapy(PDT) and photothermal therapy (PTT), is a promisingmethod of tumor treatment, which has the advantages ofstrong specificity and small side effects. However, PDT willaggravate the hypoxic environment in tumor cells, and PTTwill lead to heat-resistant reaction, both of which will make theorganism quickly produce heat shock proteins (HSPs) toprotect itself, thus seriously hindering the therapeuticefficiency of phototherapy. As a natural HSPs inhibitor,quercetin (QR) provides a feasible way to solve this problem.Herein, a kind of metal organic framework (MOF), Fe-TCPP(FT), was used as a delivery material and photosensitizer tobuild a chemo-phototherapy platform, and QR was used as achemotherapy drug and HSPs inhibitor. On this basis, the nanoparticles (NPs) were modified with PEG-CPP30 (a cellpenetratingpeptide that specifically recognizes human breast cancer MCF-7 cells), which showed excellent targetingcapacity and biocompatibility. The combination of chemotherapy and phototherapy significantly improved the anti-cancereffect. At the same time, NPs also showed prominent anti-HSPs effect. The effective connection of the two played acomplementary role in the process of tumor treatment, which provided a new strategy for the accurate and efficienttreatment of tumors in the future.
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).
文摘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.
