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:Lipid-Based Nanoparticles Fused with Natural Killer Cell Plasma Membrane Proteins for Triple-Negative Breast Cancer Therapy.
Lipid-Based Nanoparticles Fused with Natural Killer Cell Plasma Membrane Proteins for Triple-Negative Breast Cancer Therapy.
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免疫疗法结合化学药物和基因工程工具正成为一种有前景的三阴性乳腺癌(TNBC)治疗策略,TNBC比其他乳腺癌亚型更具侵袭性且进展更差。在本研究中,基于脂质的纳米颗粒(LNPs)具有类似NK细胞的功能,能够递送肿瘤特异性治疗药物并抑制肿瘤生长。融合NK细胞膜蛋白系统的LNPs(NK-LNP)具有三个主要特征:(i)亲水性质粒DNA封装在LNPs内并递送至细胞时,可抑制TNBC转移;(ii)LNPs的脂质组成,包括C18神经酰胺,具有抗癌作用;(iii)NK细胞膜蛋白固定在LNP表面,能够靶向递送至TNBC细胞。这些颗粒促进了HIC1质粒DNA的靶向递送和免疫细胞功能的调节。递送的治疗基因可以抑制TNBC转移,进而诱导凋亡性细胞死亡,同时靶向巨噬细胞以促进细胞因子释放。这种抗癌效果有望应用于治疗各种难以治疗的癌症,通过融合NK细胞质膜蛋白的LNP,可同时递送治疗性化学药物和基因。
Immunotherapy combined with chemicals and genetic engineering tools is emerging as a promising strategy to treat triple-negative breast cancer (TNBC), which is more aggressive with poorer progress than other breast cancer subtypes. In this study, lipid-based nanoparticles (LNPs) possessed an NK cell-like function that could deliver tumor-specific therapeutics and inhibit tumor growth. LNPs fused with an NK cell membrane protein system (NK-LNP) have three main features: (i) hydrophilic plasmid DNA can inhibit TNBC metastasis when encapsulated within LNPs and delivered to cells; (ii) the lipid composition of LNPs, including C18 ceramide, exhibits anticancer effects; (iii) NK cell membrane proteins are immobilized on the LNP surface, enabling targeted delivery to TNBC cells.
These particles facilitate the targeted delivery of HIC1 plasmid DNA and the modulation of immune cell functions. Delivered therapeutic genes can inhibit metastasis of TNBC and then induce apoptotic cell death while targeting macrophages to promote cytokine release. The anticancer effect is expected to be applied in treating various difficult-to-treat cancers with LNP fused with NK cell plasma membrane proteins, which can simultaneously deliver therapeutic chemicals and genes.
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