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NHF 衍生碳点:乳腺癌治疗中的预验证方法。

NHF-derived carbon dots: prevalidation approach in breast cancer treatment.

机构信息

Regional Institute of Oncology, TRANSCEND Center, 700483, Iasi, Romania.

Department of Immunology, "Gr.T.Popa" University of Medicine and Pharmacy, 700115, Iasi, Romania.

出版信息

Sci Rep. 2020 Jul 29;10(1):12662. doi: 10.1038/s41598-020-69670-z.

DOI:10.1038/s41598-020-69670-z
PMID:32728167
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7391642/
Abstract

Metastatic breast cancer dominates the female cancer-related mortality. Tumour-associated molecules represents a crucial for early disease detection and identification of novel therapeutic targets. Nanomaterial technologies provide promising novel approaches to disease diagnostics and therapeutics. In the present study we extend the investigations of antitumoral properties of Carbon Dots prepared from N-hydroxyphthalimide (CD-NHF) precursor. We evaluate the effect of CD-NHF on tumour cell migration and invasion in vitro and their impact on tumour progression using an in vivo model. Furthermore, we investigate the molecular mechanisms involved in CD-NHF antitumour effects. In vivo mammary tumours were induced in Balb/c female mice by injecting 4T1 cells into the mammary fat pad. Conditional treatment with CD-NHF significantly impair both migration and invasion of metastatic breast cancer cells. The presence of CD-NHF within the 3D cell cultures strongly inhibited the malignant phenotype of MDA-MB-231, 4T1 and MCF-7 cells in 3D culture, resulting in culture colonies lacking invasive projections and reduction of mammospheres formation. Importantly, breast tumour growth and metastasis dissemination was significantly reduced upon CD-NHF treatments in a syngeneic mouse model and is associated with down-regulation of Ki67 and HSP90 expression. CD-NHF nanostructures provide exciting perspective for improving treatment outcome in breast cancer.

摘要

转移性乳腺癌是女性癌症相关死亡的主要原因。肿瘤相关分子是早期疾病检测和新治疗靶点识别的关键。纳米材料技术为疾病诊断和治疗提供了有前途的新方法。在本研究中,我们扩展了对 N-羟基邻苯二甲酰亚胺(CD-NHF)前体制备的碳点的抗肿瘤特性的研究。我们评估了 CD-NHF 对体外肿瘤细胞迁移和侵袭的影响,并使用体内模型评估其对肿瘤进展的影响。此外,我们研究了 CD-NHF 抗肿瘤作用涉及的分子机制。通过将 4T1 细胞注入乳腺脂肪垫,在 Balb/c 雌性小鼠中诱导体内乳腺肿瘤。条件性给予 CD-NHF 可显著抑制转移性乳腺癌细胞的迁移和侵袭。在 3D 细胞培养物中存在 CD-NHF 强烈抑制 MDA-MB-231、4T1 和 MCF-7 细胞的恶性表型,导致培养物菌落缺乏侵袭性突起,并减少乳腺球体形成。重要的是,在同种小鼠模型中,CD-NHF 处理可显著减少乳腺癌肿瘤生长和转移扩散,并与 Ki67 和 HSP90 表达下调相关。CD-NHF 纳米结构为改善乳腺癌治疗效果提供了令人兴奋的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/4de0413821bb/41598_2020_69670_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/d237ff0f932a/41598_2020_69670_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/c7bdcb18a3a0/41598_2020_69670_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/f08705856f56/41598_2020_69670_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/e65a7217537c/41598_2020_69670_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/eda52f8315ba/41598_2020_69670_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/1f9453b67be7/41598_2020_69670_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/6902be1a50ce/41598_2020_69670_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/4de0413821bb/41598_2020_69670_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/d237ff0f932a/41598_2020_69670_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/c7bdcb18a3a0/41598_2020_69670_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/f08705856f56/41598_2020_69670_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/e65a7217537c/41598_2020_69670_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/eda52f8315ba/41598_2020_69670_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/1f9453b67be7/41598_2020_69670_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/6902be1a50ce/41598_2020_69670_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfed/7391642/4de0413821bb/41598_2020_69670_Fig8_HTML.jpg

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