应用肿瘤靶向介孔硅纳米颗粒传递miR-200c-3p在乳腺癌治疗中的研究。
Delivery of miR-200c-3p Using Tumor-Targeted Mesoporous Silica Nanoparticles for Breast Cancer Therapy.
发表日期:2023 Aug 07
作者:
Iris Garrido-Cano, Anna Adam-Artigues, Ana Lameirinhas, Juan F Blandez, Vicente Candela-Noguera, Ana Lluch, Begoña Bermejo, Felix Sancenón, Juan Miguel Cejalvo, Ramón Martínez-Máñez, Pilar Eroles
来源:
Cellular & Molecular Immunology
摘要:
尽管乳腺癌治疗取得了一定的进步,但仍然是全球妇女死于癌症的首要原因。在这种背景下,微小RNA已成为潜在的治疗靶点,但在体内应用方面仍存在一些限制。特别是,miR-200c-3p是一种众所周知的抑癌微小RNA,通过下调ZEB1和ZEB2来抑制乳腺癌的肿瘤进展和转移。基于上述情况,我们描述了使用介孔二氧化硅纳米粒子设计和验证miR-200c-3p输送的纳米设备。我们证明了合成纳米设备的生物相容性以及它们能够逃逸内体源/溶酶体并在体外抑制肿瘤细胞的肿瘤发生、侵袭、迁移和增殖能力。此外,在一个原位乳腺癌小鼠模型中,证实了纳米粒子对肿瘤的定位和miR-200c-3p的有效输送,并通过肿瘤大小和肺转移的减少,而无毒性征象,证明了治疗效果。综上所述,我们的结果提供了miR-200c-3p负载纳米粒子作为乳腺癌治疗的潜在策略,并且是一种安全有效的肿瘤靶向性微小RNA输送系统的证据。
Despite advances in breast cancer treatment, it remains the leading cause of cancer-related death in women worldwide. In this context, microRNAs have emerged as potential therapeutic targets but still present some limitations for in vivo applications. Particularly, miR-200c-3p is a well-known tumor suppressor microRNA that inhibits tumor progression and metastasis in breast cancer through downregulating ZEB1 and ZEB2. Based on the above, we describe the design and validation of a nanodevice using mesoporous silica nanoparticles for miR-200c-3p delivery for breast cancer treatment. We demonstrate the biocompatibility of the synthesized nanodevices as well as their ability to escape from endosomes/lysosomes and inhibit tumorigenesis, invasion, migration, and proliferation of tumor cells in vitro. Moreover, tumor targeting and effective delivery of miR-200c-3p from the nanoparticles in vivo are confirmed in an orthotopic breast cancer mouse model, and the therapeutic efficacy is also evidenced by a decrease in tumor size and lung metastasis, while showing no signs of toxicity. Overall, our results provide evidence that miR-200c-3p-loaded nanoparticles are a potential strategy for breast cancer therapy and a safe and effective system for tumor-targeted delivery of microRNAs.