Su Xiaohan, Luo Yunbo, Wang Yali, Qu Peng, Liu Jun, Han Shiqi, Ma Cui, Deng Shishan, Liang Qi, Qi Xiaowei, Cheng Panke, Hou Lingmi
Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Breast Surgery, Mianyang 404 hospital, Mianyang, China.
Mater Today Bio. 2025 Jan 19;31:101497. doi: 10.1016/j.mtbio.2025.101497. eCollection 2025 Apr.
Triple-negative breast cancer (TNBC) is the most malignant type of breast cancer and lacks effective targeted therapeutic drugs, resulting in a high recurrence rate and worse outcome. In this study, bioinformatic analysis and a series of experiments demonstrated that MOCR2 was highly expressed in TNBC and closely associated with poor prognosis, indicating that MOCR2 may be a potential therapeutic target for TNBC. Subsequently, Angoline was identified as an inhibitor of MORC2 protein by high-throughput screening and can significantly kill the TNBC cells by blocking cell cycle and inducing apoptosis. Furthermore, the biomimetic nanodrug delivery system (PMD) was designed by encapsulating tetrahedral DNA nanostructures with biomimetic cell membrane, and it can efficiently evade the phagocytosis of immune system and target TNBC tissue. Additionally, PMD can markedly enhance the killing effect of Angoline on TNBC tumors. Therefore, PMD-enveloped Angoline provide a highly effective targeted therapeutic regimen for TNBC and may improve the outcome for patients with TNBC.
三阴性乳腺癌（TNBC）是最恶性的乳腺癌类型，缺乏有效的靶向治疗药物，导致复发率高且预后较差。在本研究中，生物信息学分析和一系列实验表明，MORC2在TNBC中高表达且与不良预后密切相关，这表明MORC2可能是TNBC的一个潜在治疗靶点。随后，通过高通量筛选确定Angoline为MORC2蛋白的抑制剂，它可通过阻断细胞周期和诱导凋亡来显著杀伤TNBC细胞。此外，通过用仿生细胞膜包裹四面体DNA纳米结构设计了仿生纳米药物递送系统（PMD），它能有效逃避免疫系统的吞噬并靶向TNBC组织。此外，PMD可显著增强Angoline对TNBC肿瘤的杀伤作用。因此，PMD包裹的Angoline为TNBC提供了一种高效的靶向治疗方案，并可能改善TNBC患者的预后。
