Abstract
Melanoma treatment has been revolutionized with the development of targeted therapies and im-munotherapies,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 treat-ment.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 trig-gered MFO degradation to induce Mn2+and Fe3+release.On one hand,Mn2+blocked G1/S phase through the activation of p27 pathway.On the other hand,Fe3+could arrest the G2/M phase by upregulating the polo-like kinase 4(PLK4)expression as well as inhibiting autolysosome formation to achieve the en-hanced cell cycle arrest,thereby promoting the apoptosis of melanoma cells.In summary,this study pro-posed 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 anti-tumor efficacy.
维普
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