Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor
Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor
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DOI：
10.1021/acs.nanolett.7b03206
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发表时间：
2018-08-01
期刊：
影响因子：
10.8
通讯作者：
Barlev, Nickolai A.
中科院分区：
文献类型：
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作者：
Canfarotta, Francesco;Lezina, Larissa;Barlev, Nickolai A.
表皮生长因子受体(EGFR)是一种酪氨酸激酶受体，在许多肿瘤中过度表达，包括近一半的三阴性乳腺癌。后者属于一种非常具侵袭性和抗药性的恶性肿瘤。尽管人源化的抗EGFR抗体作为单一疗法或与遗传毒性药物联合使用可以有效地对抗这些癌症，但它们在临床应用中的一些已知缺点是不稳定和生产成本高。此外，开发针对膜蛋白的抗体是一项非常具有挑战性的任务。因此，当前工作的主要焦点是设计超分子药物，用于靶向癌细胞中的膜蛋白，从而实现更具特异性的阻力输送。它们是用一种基于固相法制备分子印迹聚合物纳米颗粒(NanMIP)的新型双印迹方法制备的，该纳米颗粒负载阿霉素并靶向EGFR的线性表位。此外，在结合时，阿霉素负载的抗EGFR纳米MIPs只在那些过度表达EGFR的细胞中诱导细胞毒性和凋亡。因此，这种方法可以提供一种看似合理的替代传统抗体的方法，并为此类材料针对临床相关靶点的治疗应用建立了一种新的范例。此外，纳米分子印迹聚合物可以促进针对膜蛋白等困难靶点的细胞成像工具的发展。
Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is over-expressed in many tumors, including almost half of triple-negative breast cancers. The latter belong to a very-aggressive and drug-resistant form of malignancy. Although humanized anti-EGFR antibodies can work efficiently against these cancers both as monotherapy and in combination with genotoxic drugs, instability and high production costs are some of their known drawbacks in clinical use. In addition, the development of antibodies to target membrane proteins is a very challenging task. Accordingly, the main focus of the present work is the design of supramolecular agents for the targeting of membrane proteins in cancer cells and, hence, more-specific drag delivery. These were produced using a novel double-imprinting approach based on the solid-phase method for preparation of molecularly imprinted polymer nanoparticles (nanoMIPs), which were loaded with doxorubicin and targeted toward a linear epitope of EGFR. Additionally, upon binding, doxorubicin-loaded anti-EGFR nanoMIPs elicited cytotoxicity and apoptosis only in those cells that over-expressed EGFR. Thus, this approach can provide a plausible alternative to conventional antibodies and sets up a new paradigm for the therapeutic application of this class of materials against clinically relevant targets. Furthermore, nanoMIPs can promote the development of cell imaging tools against difficult targets such as membrane proteins.