Department of Chemical and Biomolecular Engineering , Sogang University , 35 Baekbeom-ro (Sinsu-dong) , Mapo-gu, Seoul 121-742 , Republic of Korea.
Department of Chemical Engineering , Kwangwoon University , 20 Kwangwoon-ro , Nowon-gu, Seoul 01897 , Republic of Korea.
ACS Appl Mater Interfaces. 2019 Mar 6;11(9):8779-8788. doi: 10.1021/acsami.8b16925. Epub 2019 Feb 15.
Nanoparticle-based cell differentiation therapy has attracted increasing research interest as it is a promising substitute for conventional cancer treatment methods. Here, the topological insulator bismuth selenide nanoparticle (BiSe NP) was core-shelled with silver (Ag@BiSe) to represent remarkable biocompatibility and plasmonic features (ca. 2.3 times higher than those of Ag nanoparticle). Moreover, a newly developed RNA three-way junction (3WJ) structure was designed for the quad-functionalization of any type of nanoparticle and surface. One leg of the 3WJ was attached to the Ag@BiSe, and the other leg harbored a cell-penetrating RNA and a florescence tag. The third leg was designed to inhibit micro-RNA-17 (miR-17) and to further release retinoic acid (RA). A new drug delivery mechanism was developed for the slow release of RA inside the cytosol based on the prerequisite inhibition of miR-17 using a strand displacement strategy. In this paper, we report a simple methodology for resolving the hydrophobicity challenges of RA by its conjugation with a RNA strand (RA/R) through a stimulus-responsive cross-linker. The developed nanobiohybrid material could fully differentiate SH-SY5Y cancer cells into neurons and stop their growth in 6 days without requiring sequential treatments which has not been reported yet. Using a surface-enhanced Raman spectroscopy technique, the RA delivery and the cell differentiation process were monitored nondestructively in real time. The fabricated nanobiohybrid material could open the new horizons in the fabrication of different diagnostic/therapeutic agents.
基于纳米颗粒的细胞分化疗法因其是传统癌症治疗方法的有前途的替代品而引起了越来越多的研究兴趣。在这里，拓扑绝缘体硒化铋纳米颗粒（BiSe NP）被银（Ag@BiSe）核壳化，以代表显著的生物相容性和等离子体特性（约比银纳米颗粒高 2.3 倍）。此外，还设计了一种新开发的 RNA 三链结（3WJ）结构，用于任何类型的纳米颗粒和表面的四官能化。3WJ 的一条腿连接到 Ag@BiSe，另一条腿携带穿透细胞的 RNA 和荧光标记。第三条腿被设计用来抑制 micro-RNA-17（miR-17），并进一步释放维甲酸（RA）。基于使用链置换策略抑制 miR-17 的前提，开发了一种新的药物输送机制，用于在细胞质内缓慢释放 RA。在本文中，我们报告了一种简单的方法，通过使用响应性交联剂将 RA 与 RNA 链（RA/R）缀合来解决 RA 的疏水性挑战。所开发的纳米生物混合材料能够在 6 天内将 SH-SY5Y 癌细胞完全分化为神经元并停止其生长，而无需进行尚未报道的序贯治疗。使用表面增强拉曼光谱技术，可以实时非破坏性地监测 RA 的递送和细胞分化过程。所制造的纳米生物混合材料可以为制造不同的诊断/治疗剂开辟新的前景。
