Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Jiangsu 221004, Xuzhou, China.
School of Medical Technology, Xuzhou Medical University, Jiangsu 221002, Xuzhou, China.
Anal Chem. 2021 Oct 19;93(41):13755-13764. doi: 10.1021/acs.analchem.1c01338. Epub 2021 Oct 5.
A multifunctional theranostic nanosystem that integrates dynamic monitoring and therapeutic functions is necessary for precision tumor medicine. Herein, an entropy-driven self-assembly nanomachine is developed that overcomes the mechanism differences of different diagnostic modes and is applied to miRNA surface-enhanced Raman scattering (SERS)-fluorescence dual-mode dynamic monitoring and synergy phototherapy. It is worth noting that the activated dual-mode theranostic nanosystem (DTN) is capable of tumor in situ fluorescence imaging and SERS absolute quantification of the target. After being internalized into tumor cells, the DTN nanosystem is activated by the DNA cascade chain displacement of the target miR-21, resulting in the secondary release of fluorophores and the assembly of core-satellite structures (CS structures). The coupling of localized surface plasmon resonances (LSPRs) in the CS structure results in the formation of numerous enhanced electric fields (hot spot) in the nanogap of the CS structure. Then the DTN nanosystem greatly improves the sensitivity and repeatability of Raman detection by converting trace targets into numerous adenines residing in the electromagnetic hot spot of the CS structure. Meanwhile, the CS structure and the loaded photosensitizer are used for synergy phototherapy under the guidance of fluorescence imaging. This proposed strategy is confirmed by in vivo and in vitro results, and it provides new ideas for tumor SERS-fluorescence dual-mode diagnosis and effective tumor therapy.
一种多功能的治疗一体化纳米系统,将动态监测和治疗功能集于一体,是精准肿瘤医学所必需的。在此,开发了一种熵驱动的自组装纳米机器,它克服了不同诊断模式的机制差异,并应用于 miRNA 表面增强拉曼散射(SERS)-荧光双模动态监测和协同光疗。值得注意的是,激活的双模治疗一体化纳米系统(DTN)能够对肿瘤进行原位荧光成像和目标物的 SERS 绝对定量。进入肿瘤细胞后,DTN 纳米系统被靶 miR-21 的 DNA 级联链置换激活,导致荧光团的二次释放和核-卫星结构(CS 结构)的组装。CS 结构中的局域表面等离子体共振(LSPR)的耦合导致 CS 结构纳米间隙中形成大量增强电场(热点)。然后,DTN 纳米系统通过将痕量靶物转换为 CS 结构电磁热点中的大量腺嘌呤,极大地提高了拉曼检测的灵敏度和重复性。同时,在荧光成像的指导下,CS 结构和负载的光敏剂用于协同光疗。该策略通过体内和体外结果得到证实,为肿瘤 SERS-荧光双模诊断和有效肿瘤治疗提供了新的思路。