Bacterial outer membrane vesicles(OMVs)are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine.In this study,OMVs are demonstrated as promising antitumo...Bacterial outer membrane vesicles(OMVs)are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine.In this study,OMVs are demonstrated as promising antitumor therapeutics.OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity,but the therapeutic window of OMVs is narrow for its toxicity.We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6(Ce6)and chemotherapeutic drug doxorubicin(DOX)into OMVs as a therapeutic platform.We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform,providing combinational photodynamic/chemo-/immunotherapy,eradicates triple-negative breast tumors in mice without side effects.Importantly,this strategy also effectively prevents tumor metastasis to the lung.This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.展开更多
基金supported by the Hunan Provincial Science and Technology Plan(No.2016TP2002).
文摘Bacterial outer membrane vesicles(OMVs)are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine.In this study,OMVs are demonstrated as promising antitumor therapeutics.OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity,but the therapeutic window of OMVs is narrow for its toxicity.We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6(Ce6)and chemotherapeutic drug doxorubicin(DOX)into OMVs as a therapeutic platform.We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform,providing combinational photodynamic/chemo-/immunotherapy,eradicates triple-negative breast tumors in mice without side effects.Importantly,this strategy also effectively prevents tumor metastasis to the lung.This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.
