Synthesis and Analysis of 64Cu-Labeled GE11-Modified Polymeric Micellar Nanoparticles for EGFR-Targeted Molecular Imaging in a Colorectal Cancer Model.,Molecular Pharmaceutics

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Synthesis and Analysis of 64Cu-Labeled GE11-Modified Polymeric Micellar Nanoparticles for EGFR-Targeted Molecular Imaging in a Colorectal Cancer Model.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-04-01 , DOI: 10.1021/acs.molpharmaceut.9b01043
Igor Paiva ₁ , Stephanie Mattingly ₂ , Melinda Wuest _{2,

3} , Samantha Leier ₂ , Mohammad Reza Vakili ₁ , Michael Weinfeld ₂ , Afsaneh Lavasanifar _{1,

4} , Frank Wuest _{1,

2,

3}

Affiliation

Polymeric micellar nanoparticles represent versatile and biocompatible platforms for targeted drug delivery. However, tracking their biodistribution, stability, and clearance profile in vivo is challenging. The goal of this study was to prepare surface-modified micelles with peptide GE11 for targeting the epidermal growth factor receptor (EGFR). In vitro fluorescence studies demonstrated significantly higher internalization of GE11 micelles into EGFR-expressing HCT116 colon cancer cells versus EGFR-negative SW620 cells. Azo coupling chemistry of tyrosine residues in the peptide backbone with aryl diazonium salts was used to label the micelles with radionuclide 64Cu for positron emission tomography (PET) imaging. In vivo analysis of 64Cu-labeled micelles showed prolonged blood circulation and predominant hepatobiliary clearance. The biodistribution profile of EGFR-targeting GE11 micelles was compared with nontargeting HW12 micelles in HCT116 tumor-bearing mice. PET revealed increasing tumor-to-muscle ratios for both micelles over 48 h. Accumulation of GE11-containing micelles in HCT116 tumors was higher compared to HW12-decorated micelles. Our data suggest that the efficacy of image-guided therapies with micellar nanoparticles could be enhanced by active targeting, as demonstrated with cancer biomarker EGFR.

中文翻译：

大肠癌模型中EGFR靶向分子成像的64Cu标记GE11修饰的聚合物胶束纳米颗粒的合成与分析。

聚合胶束纳米颗粒代表了靶向药物递送的多功能和生物相容性平台。但是，在体内追踪其生物分布，稳定性和清除率曲线具有挑战性。这项研究的目的是用肽GE11制备表面修饰的胶束，以靶向表皮生长因子受体（EGFR）。体外荧光研究表明，与EGFR阴性SW620细胞相比，GE11胶束在表达EGFR的HCT116结肠癌细胞中的内化程度明显更高。肽主链上的酪氨酸残基与芳基重氮盐的偶氮偶联化学用于放射性核素64Cu标记胶束，用于正电子发射断层扫描（PET）成像。体内分析64Cu标记的胶束显示血液循环延长和肝胆清除率居高不下。在荷HCT116荷瘤小鼠中比较了靶向EGFR的GE11胶束和非靶向HW12胶束的生物分布特征。PET显示，在48小时内，两个胶束的肿瘤与肌肉之比均增加。与装饰有HW12的胶束相比，HCT116肿瘤中含有GE11的胶束的积累更高。我们的数据表明，胶束状纳米颗粒的图像引导疗法的功效可以通过主动靶向来增强，如癌症生物标志物EGFR所证明的。

更新日期：2020-04-01

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