期刊
BIOACTIVE MATERIALS
卷 20, 期 -, 页码 548-560出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2022.05.037
关键词
Bacterial outer membrane vesicles; Bioengineering; Drug delivery; Macrophage; Pyroptosis; Tumor microenvironment
This study demonstrates the potential of using OMVs as antitumor therapeutics. By co-loading photosensitizer and chemotherapeutic drugs into OMVs and enhancing tumor-targeting ability through macrophage-mediated delivery, a combination of photodynamic therapy, chemotherapy, and immunotherapy can be achieved, effectively eradicating breast tumors and preventing tumor metastasis.
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.
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