摘要
The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer.In present study,nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2(MMP-2)dual-responsive,tumor targeting,and size-variability were designed for enhancing the antitumor efficacy and achieving"on-demand"drug release markedly.Based on the thermal sensitivity of gelatin,we designed a size-variable gelatin nanoparticle(GNP)to encapsulate indocyanine green(ICG)and doxorubicin(DOX).Under an 808 nm laser irradiation,GNP-DOX/ICG responded photothermally and swelled in size from 71.58?4.28 to 160.80?9.51 nm,which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics.Additionally,GNP-DOX/ICG showed a size reduction of the particles to 33.24?4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor.In the subsequently performed in vitro experiments,it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic.Consequently,GNP-DOX/ICG could efficiently suppress the growth of 4 T1 tumor in vivo.In conclusion,this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.
基金
supported by the National Natural Science Foundation of China(81873014,China)
Natural Science Foundation of Zhejiang Province(LQ18E030003,China)
China Postdoctoral Science Foundation(2017M621890,China)
the Science and Technology Innovation Team Project of Zhejiang Province(2019R410057,China)
