Biomedical Research Institute INCLIVA, Valencia 46010, Spain.
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia 46010, Spain.
ACS Appl Mater Interfaces. 2023 Aug 16;15(32):38323-38334. doi: 10.1021/acsami.3c07541. Epub 2023 Aug 7.
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 applications. Particularly, miR-200c-3p is a well-known tumor suppressor microRNA that inhibits tumor progression and metastasis in breast cancer through downregulating and . 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 . Moreover, tumor targeting and effective delivery of miR-200c-3p from the nanoparticles 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.
尽管乳腺癌治疗取得了进展，但它仍然是全球女性癌症相关死亡的主要原因。在这种情况下，microRNAs 已成为潜在的治疗靶点，但在应用中仍存在一些局限性。特别是，miR-200c-3p 是一种众所周知的肿瘤抑制 microRNA，通过下调和抑制乳腺癌的肿瘤进展和转移。基于上述内容，我们描述了一种使用介孔硅纳米粒子进行 miR-200c-3p 递送来治疗乳腺癌的纳米器件的设计和验证。我们证明了合成纳米器件的生物相容性以及它们逃避内涵体/溶酶体并抑制肿瘤发生、侵袭、迁移和肿瘤细胞增殖的能力。此外，在原位乳腺癌小鼠模型中证实了肿瘤靶向和纳米粒子中 miR-200c-3p 的有效递释，并且通过减小肿瘤体积和肺转移也证明了治疗效果，同时没有毒性迹象。总的来说，我们的结果提供了证据，表明负载 miR-200c-3p 的纳米粒子是一种有潜力的乳腺癌治疗策略，也是一种安全有效的肿瘤靶向 microRNAs 递释系统。
