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
英文原题:Herbal polysaccharide-based carrier enhances immunogenic cell death in cancer chemotherapy.
Herbal polysaccharide-based carrier enhances immunogenic cell death in cancer chemotherapy.
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乳腺癌是全球重大的健康负担,其生长和转移导致了高死亡率,凸显了对创新治疗策略的需求。本研究旨在开发负载阿霉素(Dox)的乳腺癌靶向纳米颗粒,以对抗原发肿瘤和转移。通过利用铁皮石斛多糖(DOP)——一种具有免疫调节活性的草本多糖——作为载体,并引入叶酸(FA)作为主动靶向配体,我们在化学免疫治疗方面取得了进展。将所得的FA@Dox纳米颗粒通过被动和主动靶向递送至实体瘤后,肿瘤细胞被释放的Dox杀死,而DOP增强了免疫原性细胞死亡,促进自然杀伤(NK)细胞增殖,促进树突状细胞成熟,并协同调节多种免疫细胞,防止肺转移。综合评估包括材料表征、体外和体内疗效评价、生物安全性分析以及免疫反应研究。鉴于DOP来源于药食两用的铁皮石斛,所开发的基于DOP的载体作为一种先进的纳米医学平台具有巨大前景。这为协同调节多种免疫细胞,特别是通过NK细胞增殖,放大化学免疫治疗在多种肿瘤类型中的疗效提供了广阔前景。
Breast cancer is a significant global health burden, with growth and metastasis contributing to its high mortality rate, highlighting the need for innovative treatment strategies.
This study aims to develop breast cancer-targeted nanoparticles loaded with Doxorubicin (Dox) to combat both primary tumors and metastasis. By utilizing Dendrobium officinale polysaccharide (DOP), an herb polysaccharide with immunomodulatory activity, as a carrier, and incorporating folic acid (FA) as an active targeting ligand, we've achieved advancements in chemoimmunotherapy. After delivery of resulting FA@Dox nanoparticles to solid tumors by passive and active targeting, the tumor cells were killed by released Dox, and the immunogenic cell death was enhanced by the DOP, which promotes the proliferation of natural killer (NK) cells, facilitates dendritic cell maturation, and synergistically modulates various immune cells, preventing lung metastasis.
The comprehensive assessments included material characterizations, in vitro and in vivo efficacy evaluations, biosafety analysis, and immune response studies. Given that DOP is derived from the medicinal and edible Dendrobium officinale, the developed DOP-based carrier holds great promise as an advanced nanomedicine platform. This offers promising prospects for synergistic modulation of multiple immune cells, particularly through NK cell proliferation, amplifying the efficacy of chemoimmunotherapy across diverse tumor types.
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