基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Silver nanoclusters show advantages in macrophage tracing in vivo and modulation of anti-tumor immuno-microenvironment.
Silver nanoclusters show advantages in macrophage tracing in vivo and modulation of anti-tumor immuno-microenvironment.
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基于巨噬细胞的纳米医学代表了一种新兴的强大癌症治疗策略。遗憾的是,一些障碍和挑战限制了巨噬细胞介导的纳米药物递送系统的转化应用。例如,追踪和有效递送细胞至靶向肿瘤部位仍有待克服,而由于巨噬细胞对外部刺激具有可塑性,控制其状态仍然相当困难。为解决这些关键问题,我们在此报道了一种新型银纳米簇(AgNCs),其具有优异的荧光强度,尤其是在被巨噬细胞内吞后具有持久的细胞标记稳定性,表明其在追踪基于巨噬细胞的纳米药物递送方面具有广阔的应用前景。
我们的机制研究揭示,这些优势源于AgNCs逃逸巨噬细胞内溶酶体降解。此外,AgNCs可通过toll样受体4信号通路(至少部分地)启动巨噬细胞的M1样极化。载有AgNCs的工程化巨噬细胞可用于肺转移性乳腺癌治疗,显示出对转移性肿瘤的有效靶向倾向、对肿瘤免疫微环境的显著调节以及抑制肿瘤生长。
总体而言,AgNCs训练的巨噬细胞似乎是肿瘤免疫微环境调节的一种有前景的策略,可能推广至更广泛的癌症治疗领域。
Macrophage-based nanomedicine represents an emerging powerful strategy for cancer therapy. Unfortunately, some obstacles and challenges limit the translational applications of macrophage-mediated nanodrug delivery system. For instance, tracking and effective cell delivery for targeted tumor sites remain to be overcome, and controlling the states of macrophages is still rather difficult due to their plastic nature in response to external stimuli.
To address these critical issues, here, we reported a novel type of silver nanoclusters (AgNCs) with excellent fluorescent intensity, especially long-lasting cell labeling stability after endocytosis by macrophages, indicating promising applications in tracking macrophage-based nanomedicine delivery.
Our mechanistic investigations uncovered that these merits originate from the escape of AgNCs from lysosomal degradation within macrophages.
In addition, the AgNCs would prime the M1-like polarization of macrophages (at least in part) through the toll-like receptor 4 signaling pathway. The engineered macrophages laden with AgNCs could be employed for lung metastasis breast cancer treatment, showing the effective targeting propensity to metastatic tumors, remarkable regulation of tumor immune microenvironment and inhibition of tumor growth.
Collectively, AgNC-trained macrophages appear to be a promising strategy for tumor immune-microenvironment regulation, which might be generalized to a wider spectrum of cancer therapeutics.
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