提高磁性介孔硅纳米载体的抗癌药物递送性能，以实现更有效的结直肠癌治疗。

BACKGROUND: Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs. MATERIALS AND METHODS: Herein, we designed a novel DDS based on magnetic mesoporous silica core-shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors. RESULTS: Nanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects. CONCLUSION: These results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy.

背景：通过设计智能和靶向药物传递系统（DDS）可以提高抗癌药物的传递性能。为此，评估肿瘤微环境（TME）中过表达的生物标志物对于优化 DDS 非常重要。

材料和方法：本文设计了一种基于磁性介孔硅核壳纳米粒子（SPION@MSNs）的新型 DDS，其中阿霉素（DOX）在生理 pH 下的释放被金门控器阻断。在这个平台上，我们将杂功能聚乙二醇（PEG）接枝到纳米载体的外表面上，以提高其生物相容性。最后，将上皮细胞黏附分子（EpCAM）适体作为活性靶向部分共价连接（Apt-PEG-Au@NPs-DOX），用于选择性地将药物递送至结直肠癌（CRC）细胞。对非靶向和靶向纳米载体的物理化学性质进行了全面表征。在体外测定并比较了制备的纳米载体的抗癌活性、细胞内化以及随后的细胞死亡机制。最后，在携带人 HT-29 肿瘤的免疫功能低下的 C57BL/6 小鼠中评估了纳米载体的肿瘤抑制作用、生物分布和可能的副作用。

结果：纳米载体成功合成，平均最终粒径为 58.22±8.54nm。与 EpCAM 阴性 CHO 细胞相比，靶向纳米载体在 EpCAM 阳性 HT-29 细胞中的细胞毒性和细胞摄取率更高，表明适体作为靶向剂的有效性。在人源化小鼠模型中的体内结果表明，靶向纳米载体可有效增加肿瘤部位的 DOX 积累，抑制肿瘤生长，并减少不良反应。

结论：这些结果表明，磁性核、金门控器、PEG 和适体的结合可以显著提高药物传递性能，并为有效的 CRC 治疗提供一种治疗诊断一体化的 DDS。