Zhao Zheng, Wang Jingyun, Liu Mengmeng, Li Ziqian, Cao Fei, Xu Pengfei, Fang Qi, Yang Jie, Hu Zhulong, Wu Di, Liu Rongbin, Liu Xuekui
State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.
Department of Oncology, The Second Affiliated Hospital JiangxiMedical College Nanchang University, Nanchang, China, 330000.
BMC Cancer. 2025 Mar 6;25(1):413. doi: 10.1186/s12885-025-13784-y.
Expression of the Neuropilin-1 (NRP1) is reported in malignant cells of multiple human tumor types represented as a tumor marker. Targeting NRP1 with a peptide, CK3, is used for tumor molecular imaging, raising the question of the therapeutic potential of CK2, a peptide with a CK3 backbone which enhanced targeting and tumor enrichment properties.
The tumor targeting and enrichment capacity of CK2 was detected by IncuCyte, flow cytometry and animal living imaging. To enhance its therapeutic efficacy, we developed a self-assembling peptide nanoparticles Fmoc-Gffy-AP-CK2, incorporating a peptide protective domain (Fmoc), a self-assemble domain (Gffy) and an anti-tumor peptide (AP). In vitro cellular assays and in vivo tumor-xenograft experiments were conducted to evaluate the anti-tumor effect of Fmoc-Gffy-AP-CK2.
While CK3 peptide specifically targets NRP1 in vitro and in vivo, CK2 markedly achieves stronger binding with NRP1 and higher tumor accumulation. Fmoc-Gffy-AP-CK2 exhibits a potent NRP1-dependent cytotoxic effect in vitro and in vivo. Mechanically, Fmoc-Gffy-AP-CK2 triggered caspase3/gasdermin E (GSDME)-mediated pyroptosis. Fmoc-Gffy-AP-CK2 also promotes the response rate of PD-1 checkpoint blockade.
CK2, When combined with Fmoc-Gffy-AP domain, Demonstrated high anti-tumor efficacy, Providing a novel strategy for tumor treatment.
据报道，在多种人类肿瘤类型的恶性细胞中都有神经纤毛蛋白-1（NRP1）的表达，可作为一种肿瘤标志物。用一种肽CK3靶向NRP1用于肿瘤分子成像，这就引发了一个问题，即具有增强靶向和肿瘤富集特性的、以CK3为骨架的肽CK2是否具有治疗潜力。
通过IncuCyte、流式细胞术和动物活体成像检测CK2的肿瘤靶向和富集能力。为了提高其治疗效果，我们开发了一种自组装肽纳米颗粒Fmoc-Gffy-AP-CK2，它包含一个肽保护结构域（Fmoc）、一个自组装结构域（Gffy）和一个抗肿瘤肽（AP）。进行了体外细胞实验和体内肿瘤异种移植实验，以评估Fmoc-Gffy-AP-CK2的抗肿瘤作用。
虽然CK3肽在体外和体内都能特异性靶向NRP1，但CK2与NRP1的结合更强，肿瘤蓄积更高。Fmoc-Gffy-AP-CK2在体外和体内均表现出强大的依赖NRP1的细胞毒性作用。从机制上讲，Fmoc-Gffy-AP-CK2触发了半胱天冬酶3/ Gasdermin E（GSDME）介导的细胞焦亡。Fmoc-Gffy-AP-CK2还提高了PD-1检查点阻断的反应率。
CK2与Fmoc-Gffy-AP结构域结合时，显示出高抗肿瘤疗效，为肿瘤治疗提供了一种新策略。
