用于增强黑色素瘤治疗的超声响应性靶向Nrf2的负载小干扰RNA纳米气泡

Ultrasound-Responsive Nrf2-Targeting siRNA-Loaded Nanobubbles for Enhancing the Treatment of Melanoma.

作者信息

Argenziano Monica, Bessone Federica, Dianzani Chiara, Cucci Marie Angèle, Grattarola Margherita, Pizzimenti Stefania, Cavalli Roberta

机构信息

Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy.

Department of Clinical and Biological Science, University of Turin, 10125 Turin, Italy.

出版信息

Pharmaceutics. 2022 Jan 31;14(2):341. doi: 10.3390/pharmaceutics14020341.

The siRNA-mediated inhibition of nuclear factor E2-related factor 2 (Nrf2) can be an attractive approach to overcome chemoresistance in various malignant tumors, including melanoma. This work aims at designing a new type of chitosan-shelled nanobubble for the delivery of siRNA against Nrf2 in combination with an ultrasound. A new preparation method based on a water-oil-water (W/O/W) double-emulsion was purposely developed for siRNA encapsulation in aqueous droplets within a nanobubble core. Stable, very small NB formulations were obtained, with sizes of about 100 nm and a positive surface charge. siRNA was efficiently loaded in NBs, reaching an encapsulation efficiency of about 90%. siNrf2-NBs downregulated the target gene in M14 cells, sensitizing the resistant melanoma cells to the cisplatin treatment. The combination with US favored NB cell uptake and transfection efficiency. Based on the results, nanobubbles have shown to be a promising US responsive tool for siRNA delivery, able to overcome chemoresistance in melanoma cancer cells.

小干扰RNA（siRNA）介导的核因子E2相关因子2（Nrf2）抑制作用，可能是克服包括黑色素瘤在内的各种恶性肿瘤化疗耐药性的一种有吸引力的方法。这项工作旨在设计一种新型的壳聚糖包裹纳米气泡，用于在超声辅助下递送针对Nrf2的siRNA。特意开发了一种基于水包油包水（W/O/W）双乳液的新制备方法，用于将siRNA包裹在纳米气泡核心的水滴中。获得了稳定的、非常小的纳米气泡制剂，其尺寸约为100 nm，表面带正电荷。siRNA被有效地负载到纳米气泡中，包封效率约为90%。siNrf2纳米气泡下调了M14细胞中的靶基因，使耐药黑色素瘤细胞对顺铂治疗敏感。与超声联合使用有利于纳米气泡的细胞摄取和转染效率。基于这些结果，纳米气泡已被证明是一种有前景的超声响应性siRNA递送工具，能够克服黑色素瘤癌细胞的化疗耐药性。