RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
透明质酸包覆的金纳米壳用于增强肺癌化疗-光热治疗的协同效应和免疫原性细胞反应
英文原题：Hyaluronan-coated gold nanoshells for enhanced synergistic effect and immunogenic cell response of chemo-photothermal therapy on lung cancer.
查看英文原题
Hyaluronan-coated gold nanoshells for enhanced synergistic effect and immunogenic cell response of chemo-photothermal therapy on lung cancer.
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中文摘要
肺癌（LC）是全球癌症相关死亡的主要原因，在男女两性中死亡率均最高，主要归因于吸烟。非激酶跨膜细胞表面糖蛋白 CD44 可增强 LC 细胞的迁移和侵袭，导致耐药和不良预后。
本研究构建了一种负载顺铂的金纳米壳（HCP@GNS），并整合透明质酸（HCP@GNS@HA），以增强靶向能力并实现对 LC 的化疗-光热治疗（chemo-PTT）协同效应。透明质酸（HA）包覆促进了 HCP@GNS@HA 被富含 CD44 的癌细胞摄取，同时保持了 HCP@GNS 纳米颗粒优异的光热转换能力，用于在近红外暴露下进行热疗和光热消融肿瘤组织。作为纳米载体，HCP@GNS@HA 表现出高生物相容性和血液相容性，在与 NIR 照射联合时，显示出比游离药物或单独光热治疗更强的细胞毒性，尤其是在高顺式二氨二氯铂（II）（CDDP）浓度下。由 HCP@GNS@HA 介导的 chemo-PTT 有效抑制了肿瘤生长且无不良反应，显著动员了远端肿瘤中的 B 细胞、DC 细胞、巨噬细胞、自然杀伤（NK）细胞和 NKT 细胞对抗肿瘤生长。
总之，所开发的透明质酸（HA）包覆金纳米壳可能成为纳米医学的有前景候选者，可同时应对原发性和远端 LC 生长。
展开英文摘要原文
Lung cancer (LC) is the predominant cause of cancer-related fatalities globally, with the highest death rates in both genders, primarily attributed to smoking. The non-kinase transmembrane cell surface glycoprotein, CD44, enhances LC cell migration and invasion, leading to drug resistance and an unfavorable prognosis. This research formulated a cisplatin-loaded gold nanoshell (HCP@GNS) integrated with hyaluronan (HCP@GNS@HA) to enhance targeting capability and realize a synergistic effect of chemo-photothermal therapy (chemo-PTT) against LC.
The coating of hyaluronic acid (HA) facilitated the uptake of HCP@GNS@HA into CD44-rich cancer cells, maintaining the superior photothermal conversion capacity of HCP@GNS nanoparticles for hyperthermia and photothermal eradication of tumor tissues under near-infrared exposure.
As a nanocarrier, HCP@GNS@HA exhibited high biocompatibility and hemocompatibility, showing stronger cytotoxicity than either the free drug or photothermal therapy alone when combined with NIR irradiation, especially at high cis-diamminedichloroplatinum (II) (CDDP) concentrations. The chemo-PTT mediated by HCP@GNS@HA effectively curtailed tumor growth without adverse effects, significantly mobilizing B cells, DC cells, macrophages, natural killer (NK) cells, and NKT cells in the distal tumor against tumor growth.
In conclusion, the developed hyaluronic acid (HA)-coated gold nanoshells could potentially serve as a promising candidate for nanomedicine, tackling both primary and distal LC growth.
论文信息
- 作者
- Chen KC、Yang SJ、Yang SH、Pai JA、Shieh MJ
- 第一作者单位
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.Taiwan
- 通讯作者单位
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan; Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. Electronic address: soloman@ntu.edu.tw.Taiwan
- 期刊
- International journal of biological macromolecules2025 Apr
- 原文标识
- PubMed 39837437 · DOI 10.1016/j.ijbiomac.2025.140114