Melanoma treatment has been revolutionized with the development of targeted therapies and immunotherapies,which shows a positive influence on the patients.However,the long-term efficaciousness of such therapy is restr...Melanoma treatment has been revolutionized with the development of targeted therapies and immunotherapies,which shows a positive influence on the patients.However,the long-term efficaciousness of such therapy is restricted by side effects,limited clinical effects as well as quick resistance to treatment.In this work,we prepared magnetocaloric carrier-free bimetallic hydrogels,named manganese-iron oxide nanocubes@polyethylene glycol-hydrogels(MFO@PEG-Gels),to realize ion-interferential cell cycle arrest for melanoma treatment.In detail,the tumor site was exposed to alternating magnetic field(AMF)after intratumorally injected MFO@PEG-Gels,which generated hyperthermia and promoted the sol-gel phase transition for MFO sustained release.Under the tumor microenvironment,hydrogen peroxide triggered MFO degradation to induce Mn^(2+)and Fe^(3+)release.On one hand,Mn^(2+)blocked G1/S phase through the activation of p27 pathway.On the other hand,Fe^(3+)could arrest the G2/M phase by upregulating the polo-like kinase 4(PLK4)expression as well as inhibiting autolysosome formation to achieve the enhanced cell cycle arrest,thereby promoting the apoptosis of melanoma cells.In summary,this study proposed ion-interferential cell cycle arrest strategy by a multifunctional and injectable magnetic bimetallic hydrogel for melanoma treatment,which provided a secure and sustainable regimen for enhancing antitumor efficacy.展开更多
基金supported by National Natural Science Foundation of China(No.82273873)Young Elite Scientists Sponsorship Program by Tianjin(No.0701320001)+2 种基金Major Special Projects(No.0402080005)Natural Science Foundation of Tianjin(No.21JCYBJC00660)Young Program Natural Science Foundation of Tianjin(No.20JCQNJC01610)。
文摘Melanoma treatment has been revolutionized with the development of targeted therapies and immunotherapies,which shows a positive influence on the patients.However,the long-term efficaciousness of such therapy is restricted by side effects,limited clinical effects as well as quick resistance to treatment.In this work,we prepared magnetocaloric carrier-free bimetallic hydrogels,named manganese-iron oxide nanocubes@polyethylene glycol-hydrogels(MFO@PEG-Gels),to realize ion-interferential cell cycle arrest for melanoma treatment.In detail,the tumor site was exposed to alternating magnetic field(AMF)after intratumorally injected MFO@PEG-Gels,which generated hyperthermia and promoted the sol-gel phase transition for MFO sustained release.Under the tumor microenvironment,hydrogen peroxide triggered MFO degradation to induce Mn^(2+)and Fe^(3+)release.On one hand,Mn^(2+)blocked G1/S phase through the activation of p27 pathway.On the other hand,Fe^(3+)could arrest the G2/M phase by upregulating the polo-like kinase 4(PLK4)expression as well as inhibiting autolysosome formation to achieve the enhanced cell cycle arrest,thereby promoting the apoptosis of melanoma cells.In summary,this study proposed ion-interferential cell cycle arrest strategy by a multifunctional and injectable magnetic bimetallic hydrogel for melanoma treatment,which provided a secure and sustainable regimen for enhancing antitumor efficacy.
