School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Biomater Sci. 2023 Jul 25;11(15):5301-5319. doi: 10.1039/d3bm00555k.
Liver cancer (LC), one of the most common malignant primary tumors, presents a poor prognosis, high morbidity rate, and poor clinical outcomes. Despite conventional treatments have been applied prior to the deterioration, their clinical benefits were still limited. Arsenic trioxide (ATO), a toxic Chinese medicine, has been proven to efficiently inhibit the growth of LC both and . However, its therapeutic effects are hindered by poor pharmacokinetics and dose-limited toxicity. In this study, we developed a pH-responsive nanoplatform (PEG-MSN@ATO) consisting of mesoporous silica nanoparticles (MSN) that were modified with amino groups, loaded with ATO, and grafted with PEG to achieve the pH-triggered release and regulate CD8 T cells and T cells in the tumor microenvironment (TME). PEG-MSN@ATO were characterized by uniform size, good loading efficiency, pH-responsive release features, decreased macrophage uptake, and enhanced dendritic cell activation . Furthermore, studies demonstrated that PEG-MSN@ATO enhanced the antitumor efficacy by inducing apoptosis and ROS production, inhibiting tumor cell proliferation and metastasis, and activating antitumor immunity within the TME. PEG-MSN@ATO also reduced the system toxicity of ATO by controlling the pH-trigger release in the tumor site. These results indicate that the PEG-MSN@ATO represents a promising drug delivery platform for reducing toxicity and enhancing the therapeutic efficacy of ATO against LC.
肝癌（LC）是最常见的恶性原发性肿瘤之一，预后不良，发病率高，临床结局差。尽管在病情恶化之前已经采用了常规治疗，但它们的临床获益仍然有限。三氧化二砷（ATO）是一种有毒的中药，已被证明能有效抑制 LC 的生长。然而，其治疗效果受到药代动力学不佳和剂量限制毒性的阻碍。在本研究中，我们开发了一种 pH 响应纳米平台（PEG-MSN@ATO），由经过氨基修饰的介孔硅纳米粒子（MSN）组成，负载 ATO，并接枝 PEG，以实现 pH 触发释放，并调节肿瘤微环境（TME）中的 CD8 T 细胞和 T 细胞。PEG-MSN@ATO 的特点是粒径均匀、载药效率高、pH 响应释放特性、巨噬细胞摄取减少、树突状细胞激活增强。此外，研究表明，PEG-MSN@ATO 通过诱导细胞凋亡和 ROS 产生、抑制肿瘤细胞增殖和转移以及激活 TME 中的抗肿瘤免疫来增强抗肿瘤功效。PEG-MSN@ATO 还通过控制肿瘤部位的 pH 触发释放来降低 ATO 的系统毒性。这些结果表明，PEG-MSN@ATO 代表了一种有前途的药物递送平台，可降低 ATO 的毒性并增强其治疗 LC 的疗效。
