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抗体靶向的磷酸钙硅纳米颗粒优先被共培养的人转移性乳腺癌细胞和骨成骨细胞中的转移性三阴性乳腺癌细胞摄取。

Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.

机构信息

Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA.

Department of Bioengineering, The Pennsylvania State University, University Park, PA.

出版信息

Nanomedicine. 2021 Jun;34:102383. doi: 10.1016/j.nano.2021.102383. Epub 2021 Mar 13.

Abstract

Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone.

摘要

钙磷硅纳米颗粒(CPSNPs)是一种可生物吸收的纳米颗粒,可与靶向分子进行生物偶联,并将活性药物包裹其中递送至肿瘤细胞,而不会对邻近的健康组织造成损害。本研究获得的数据表明,CPSNPs 上的抗 CD71 抗体靶向这些纳米颗粒,并增强其在体外三阴性乳腺癌细胞中的内化作用。半胱天冬酶 3、7 激活、DNA 损伤和荧光显微镜证实了由靶向抗 CD71-CPSNPs 包裹的吉西他滨单磷酸盐(用于治疗包括乳腺癌和卵巢癌在内的癌症的化疗药物吉西他滨的活性代谢物)引起的乳腺癌细胞凋亡反应。与成骨细胞共培养时,带有荧光染料 Rhodamine WT 的靶向抗 CD71-CPSNPs 优先被乳腺癌细胞内化。虽然成骨细胞部分内化了抗 CD71-GemMP-CPSNPs,但它们的细胞生长不受影响。这些结果表明,CPSNPs 可作为成像工具和用于治疗转移至骨骼的乳腺癌的选择性药物递送系统。

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本文引用的文献

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CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
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