首页|Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy
Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy
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Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an acti-vated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascu-lar normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and pro-moting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.
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