{"title":"以宫颈癌为靶点的 M1 巨噬细胞膜包裹紫杉醇/β-榄香烯纳米粒子用于强化治疗","authors":"","doi":"10.1016/j.ijpx.2024.100276","DOIUrl":null,"url":null,"abstract":"<div><p>Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. β-elemene (β-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/β-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/β-ELE) for co-delivery of PTX&β-ELE. Through both <em>in vitro</em> and <em>in vivo</em> cervical cancer models, we demonstrated that M1@PLGA/PTX/β-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/β-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000483/pdfft?md5=428acdc9d41659fed71ace04dce58008&pid=1-s2.0-S2590156724000483-main.pdf","citationCount":"0","resultStr":"{\"title\":\"M1 macrophage-membrane-cloaked paclitaxel/β-elemene nanoparticles targeting cervical cancer for enhanced therapy\",\"authors\":\"\",\"doi\":\"10.1016/j.ijpx.2024.100276\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. β-elemene (β-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/β-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/β-ELE) for co-delivery of PTX&β-ELE. Through both <em>in vitro</em> and <em>in vivo</em> cervical cancer models, we demonstrated that M1@PLGA/PTX/β-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/β-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.</p></div>\",\"PeriodicalId\":14280,\"journal\":{\"name\":\"International Journal of Pharmaceutics: X\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-08-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2590156724000483/pdfft?md5=428acdc9d41659fed71ace04dce58008&pid=1-s2.0-S2590156724000483-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmaceutics: X\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590156724000483\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics: X","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590156724000483","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
宫颈癌是全球女性因癌症死亡的主要原因之一,因此迫切需要有效的治疗方案。紫杉醇(PTX)是一种天然二萜生物碱化合物,具有抑制有丝分裂和诱导肿瘤细胞程序性凋亡的作用。然而,其毒性和耐药性限制了它对某些宫颈癌患者的疗效。β-榄香烯(β-ELE)可通过抑制 ATP 结合盒转运体逆转多药耐药性,从而提高化疗药物的保留率。因此,我们建议使用 PTX/β-ELE 联合疗法来提高化疗敏感性。为了加强靶向给药,我们开发了M1-巨噬细胞-膜包被纳米颗粒(M1@PLGA/PTX/β-ELE),用于联合给药PTX&β-ELE。通过体外和体内宫颈癌模型,我们证实 M1@PLGA/PTX/β-ELE 能有效抑制肿瘤进展和肿瘤相关巨噬细胞的极化。此外,H&E染色证实了M1@PLGA/PTX/β-ELE的高度治疗生物安全性,因为在整个治疗过程中未观察到主要器官的明显损伤。总之,本研究提出了一种靶向仿生纳米平台和组合策略,可协同增强恶性肿瘤的化疗敏感性。
M1 macrophage-membrane-cloaked paclitaxel/β-elemene nanoparticles targeting cervical cancer for enhanced therapy
Cervical cancer is a leading cause of cancer-related mortality in females worldwide, necessitating urgent solutions for effective treatment. Paclitaxel (PTX), a natural diterpene alkaloid compound, has the ability to inhibit mitosis and induce programmed apoptosis in tumor cells. However, its toxicity and drug resistance limit its efficacy in certain cervical cancer patients. β-elemene (β-ELE) can reverse multidrug resistance by inhibiting ATP-binding cassette transporters, thereby enhancing chemotherapy drug retention. Therefore, we propose a combination therapy using PTX/β-ELE to improve chemotherapy sensitivity. To enhance targeted drug delivery, we developed M1-macrophage-membrane-coated nanoparticles (M1@PLGA/PTX/β-ELE) for co-delivery of PTX&β-ELE. Through both in vitro and in vivo cervical cancer models, we demonstrated that M1@PLGA/PTX/β-ELE effectively suppressed tumor progression and polarization of tumor-associated macrophages. Furthermore, H&E staining confirmed the high therapeutic biosafety of M1@PLGA/PTX/β-ELE as there was no significant damage observed in major organs throughout the entire therapeutic process. Overall, this study presents a targeted biomimetic nanoplatform and combinatorial strategy that synergistically enhances chemosensitivity in malignant tumors.