利用cd47工程细胞衍生的纳米平台靶向EGF受体治疗癌症。

IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY
Nanotechnology, Science and Applications Pub Date : 2022-07-05 eCollection Date: 2022-01-01 DOI:10.2147/NSA.S352038
Moon Jung Choi, Kang Chan Choi, Do Hyun Lee, Hwa Yeon Jeong, Seong Jae Kang, Min Woo Kim, In Ho Jeong, Young Myoung You, Jin Suk Lee, Yeon Kyung Lee, Chan Su Im, Yong Serk Park
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引用次数: 2

摘要

简介:避免吞噬细胞和减少脱靶毒性是纳米颗粒治疗药物临床应用的主要障碍。为了克服这些错误,本研究制备了表达CD47蛋白抑制免疫细胞吞噬攻击的纳米颗粒,并对其作为抗癌药物递送载体进行了评估。方法:用编码CD47的质粒转染人胚胎肾细胞质膜制备CD47+细胞源性纳米颗粒(cdn)。将多柔比星(DOX)加载到cdn中,并将抗egf受体(EGFR)抗体偶联到cdn表面,靶向过表达EGFR的肿瘤。结果:成功合成了结构稳定的CD47+iCDNs-DOX。与对照cdn相比,RAW264.7巨噬细胞对CD47+ cdn的摄取较少。抗egfr CD47+ cdn (icdn)在体外选择性识别egfr阳性的MDA-MB-231细胞,并在小鼠靶肿瘤异种移植物中更有效地积累。此外,与非靶向cdn或CD47- icdn相比,封装阿霉素(icdn -DOX)的icdn对小鼠肿瘤生长的抑制作用最高,可能是由于DOX对肿瘤组织的递送增强。讨论:这些结果表明,通过与巨噬细胞避免CD47和肿瘤靶向抗体功能化,可以促进生物相容性细胞膜源性纳米载体的临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms.

EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms.

EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms.

EGF Receptor-Targeting Cancer Therapy Using CD47-Engineered Cell-Derived Nanoplatforms.

Introduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle.

Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR.

Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs.

Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.

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来源期刊
Nanotechnology, Science and Applications
Nanotechnology, Science and Applications NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
11.70
自引率
0.00%
发文量
3
审稿时长
16 weeks
期刊介绍: Nanotechnology, Science and Applications is an international, peer-reviewed, Open Access journal that focuses on the science of nanotechnology in a wide range of industrial and academic applications. The journal is characterized by the rapid reporting of reviews, original research, and application studies across all sectors, including engineering, optics, bio-medicine, cosmetics, textiles, resource sustainability and science. Applied research into nano-materials, particles, nano-structures and fabrication, diagnostics and analytics, drug delivery and toxicology constitute the primary direction of the journal.
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