Detection and imaging of aggressive cancer cells using an epidermal growth factor receptor (EGFR)-targeted filamentous plant virus-based nanoparticle.
Detection and imaging of aggressive cancer cells using an epidermal growth factor receptor (EGFR)-targeted filamentous plant virus-based nanoparticle.
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DOI：
10.1021/bc500545z
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发表时间：
2015-02-18
影响因子：
4.7
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Chariou PL;Lee KL;Wen AM;Gulati NM;Stewart PL;Steinmetz NF
分子成像方法和靶向药物递送有望更早地检测疾病并以更高的疗效进行治疗，同时减少副作用，从而提高生存率和生活质量。基于病毒的纳米颗粒是一个很有前途的平台，因为它们的支架可以通过遗传和化学方法进行操纵，以同时显示靶向配体，同时携带用于诊断或治疗干预的有效载荷。在这里，我们展示了一个12个氨基酸的肽配体，GE 11（YHWYGYTPQNVI），在由植物病毒马铃薯病毒X（PVX）形成的纳米纤维上。生物缀合用于产生靶向表皮生长因子受体（EGFR）的荧光标记的PVX-GE 11细丝。使用人皮肤表皮样癌、结肠直肠腺癌和三阴性乳腺癌细胞系（A-431、HT-29、MDA-MB-231）证明了细胞检测和成像，所有这些细胞系都在不同程度上上调EGFR。未观察到乳腺导管癌（BT-474）细胞的非特异性摄取。此外，EGFR+癌细胞和巨噬细胞的共培养实验表明成功靶向和分配癌细胞。这项研究为开发EGFR靶向细丝提供成像和诊断造影剂和/或靶向药物递送的毒性有效载荷奠定了基础。
Molecular imaging approaches and targeted drug delivery hold promise for earlier detection of diseases and treatment with higher efficacy while reducing side effects, therefore increasing survival rates and quality of life. Virus-based nanoparticles are a promising platform because their scaffold can be manipulated both genetically and chemically to simultaneously display targeting ligands while carrying payloads for diagnosis or therapeutic intervention. Here, we displayed a 12-amino-acid peptide ligand, GE11 (YHWYGYTPQNVI), on nanoscale filaments formed by the plant virus potato virus X (PVX). Bioconjugation was used to produce fluorescently labeled PVX-GE11 filaments targeted toward the epidermal growth factor receptor (EGFR). Cell detection and imaging was demonstrated using human skin epidermoid carcinoma, colorectal adenocarcinoma, and triple negative breast cancer cell lines (A-431, HT-29, MDA-MB-231), all of which upregulate EGFR to various degrees. Nonspecific uptake in ductal breast carcinoma (BT-474) cells was not observed. Furthermore, co-culture experiments with EGFR+ cancer cells and macrophages indicate successful targeting and partitioning toward the cancer cells. This study lays a foundation for the development of EGFR-targeted filaments delivering contrast agents for imaging and diagnosis, and/or toxic payloads for targeted drug delivery.