研究概要
胃癌由于高度异质性和侵袭性强,构成了巨大的治疗挑战。
中文摘要
胃癌由于高度异质性和侵袭性强,治疗面临巨大挑战。为应对这一挑战,我们首先制备了手性Bi 2 Mo 3 O 12纳米颗粒(NPs),其在920 nm波长处表现出约160 mdeg的强圆二色性信号。值得注意的是,腹腔注射L -Bi 2 Mo 3 O 12 NPs实现了完全肿瘤清除,表现为生存期延长、体重维持和肿瘤负荷降低。在机制上,L -Bi 2 Mo 3 O 12 NPs首先通过脾脏巨噬细胞中的Toll样受体2(TLR2)激活PI3K-Akt和NF-κB信号通路,从而增加白细胞介素-6(IL-6)的产生。值得注意的是,钼价态变化产生的活性氧(ROS)进一步放大了NF-κB通路。随后,IL-6通过循环运输至肿瘤部位,激活小鼠前胃癌(MFC)细胞中的JAK-STAT信号通路,导致C-X-C基序趋化因子配体16(CXCL16)上调。该CXCL16随后招募肠道来源的3型先天淋巴细胞(ILC 3s),其提高了CXCL10表达。最终,CXCL10激活T细胞和自然杀伤(NK)细胞,从而介导肿瘤消除。这些发现凸显了L -Bi 2 Mo 3 O 12 NPs作为肿瘤免疫治疗的有前景候选物。
展开英文摘要原文
Gastric cancer poses a formidable therapeutic challenge due to high heterogeneity and aggressive invasiveness. To address this challenge, we first prepared chiral Bi 2 Mo 3 O 12 nanoparticles (NPs) that exhibited a strong circular dichroism signal of approximately 160 mdeg at 920 nm wavelength. Notably, intraperitoneal injection of L -Bi 2 Mo 3 O 12 NPs achieved complete tumor clearance, as evidenced by extended survival, maintained body weight, and reduced tumor burden. Mechanistically, L -Bi 2 Mo 3 O 12 NPs initially activated PI3K-Akt and NF-κB signaling pathways via the Toll-like receptor 2 (TLR2) in splenic macrophages, thereby increasing interleukin-6 (IL-6) production. Notably, reactive oxygen species (ROS) generated from molybdenum valence change further amplified the NF-κB pathway. Subsequently, IL-6 was transported to the tumor site via the circulation to activate the JAK-STAT signaling pathway in mouse forestomach carcinoma (MFC) cells, leading to the upregulation of C-X-C motif chemokine ligand 16 (CXCL16). This CXCL16 then recruited intestinal-derived group 3 innate lymphoid cells (ILC 3s), which elevated CXCL10 expression. Ultimately, CXCL10 activated T cells and natural killer (NK) cells, thereby mediating tumor elimination. These findings highlight L -Bi 2 Mo 3 O 12 NPs as a promising candidate for tumor immunotherapy.
论文信息
- 作者
- Huang L、Shi B、Ge Y、Xu L、Hu S、Qu A、Xu C、Sun M
- 单位
- International Joint Research Laboratory for Biointerface and Biodetection, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.China
- 期刊
- ACS nano2026 May 5