新型组蛋白去乙酰化酶抑制剂药物奇达莫德（CHI）已被证明通过表观遗传学机制调控与肿瘤发生相关的基因表达。然而，诸如非靶向性、细胞内积累差和核进入效率低等副作用严重限制了其治疗效果。双靶向纳米药物传递系统被提出作为解决方案。在这里，我们基于Prussian蓝（PB）纳米载体开发了一种载药纳米系统，结合表面增强拉曼散射（SERS）追踪功能和癌细胞/核靶向化疗能力。通过无背景SERS映射的特性，PB纳米载体可作为追踪试剂定位细胞内CHI。靶向分子的结合特异性增强了CHI载荷PB纳米载体的癌细胞/核内摄取和化疗效果。体外细胞毒性实验明确显示构建的CHI载荷PB纳米载体对Jurkat细胞的增殖具有显著抑制作用。此外，与CHI载荷PB纳米载体一起孵育的Jurkat细胞的SERS光谱分析显示明显的细胞凋亡特征：DNA骨架碎裂，染色质解聚，组蛋白乙酰化和核小体构象变化。重要的是，这种CHI载荷PB纳米载体将为淋巴母细胞白血病靶向化疗提供新的思路。版权所有 © 2023 Elsevier B.V.。保留所有权利。

The novel histone deacetylase drug chidamide (CHI) has been proven to regulate gene expression associated with oncogenesis via epigenetic mechanisms. However, huge side effects such as non-targeting, poor intracellular accumulation and low nuclear entry efficiency severely restrict its therapeutic efficacy. Dual-targeted nanodrug delivery systems have been proposed as the solution. Herein, we developed a CHI-loaded drug delivery nanosystem based on Prussian blue (PB) nanocarrier, which combines surface-enhanced Raman scattering (SERS) tracking function with cancer cell/nuclear-targeted chemotherapy capability. With the property of background-free SERS mapping, PB nanocarriers can serve as tracking agents to localize intracellular CHI. The incorporation of targeted molecules specifically enhances the cancer cell/nuclear internalization and chemotherapeutic effects of CHI-loaded PB nanocarriers. In vitro cytotoxicity assay clearly shows that the constructed CHI-loaded PB nanocarriers have significant inhibitory on Jurkat cell proliferation. Furthermore, SERS spectral analysis of Jurkat cells incubated with the CHI-loaded PB nanocarriers reveals obvious features of cellular apoptosis: DNA skeleton fragmentation, chromatin depolymerization, histone acetylation, and nucleosome conformation change. Importantly, this CHI-loaded PB nanocarrier will provide a new insight for lymphoblastic leukemia targeted chemotherapy.Copyright © 2023 Elsevier B.V. All rights reserved.