{"title":"利用外膜囊泡的组合化疗免疫疗法,通过 RGD 靶向增强癌症治疗。","authors":"Shuping Li, Xiaodong Gao","doi":"10.1016/j.nano.2022.102610","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8<sup>+</sup> T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.</p>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2022-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A combinational chemo-immune therapy using outer membrane vesicles for enhanced cancer therapy by RGD targeting.\",\"authors\":\"Shuping Li, Xiaodong Gao\",\"doi\":\"10.1016/j.nano.2022.102610\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8<sup>+</sup> T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.</p>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2022-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.nano.2022.102610\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.nano.2022.102610","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
癌症疗法因药物渗透性差而受到限制,从而阻碍了对肿瘤的有效治疗。本研究通过将诱导免疫反应的细菌外膜囊泡纳米载体和多柔比星(DOX)装入天然免疫平台 OMV 进行孵育,克服了这一难题。通过在 OMVs 表面使用靶向肽 6-Mal- Arg-Gly-Asp (RGD),增加与细胞表面整合素 αvβ3 的结合,从而提高药物在肿瘤部位的蓄积。OMV 通过减少 TAM 和 Treg、增加 CD8+ T 和 M1 以及促进 DC 成熟来逆转免疫抑制性肿瘤微环境 (TME),从而刺激免疫反应。DOX 和 OMVs 的结合弥补了单一疗法(如化疗和免疫疗法)的不足,扩大了癌症治疗的疗效,同时有助于新型纳米载体的选择和有效治疗方案的开发。
A combinational chemo-immune therapy using outer membrane vesicles for enhanced cancer therapy by RGD targeting.
Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8+ T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.
期刊介绍:
The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.
Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.