89Zr-Labeled DFO@Durvalumab-HSA nanoparticles: In vitro potential for triple-negative breast cancer

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-10-03 DOI:10.1002/ddr.22266
Fatma Yurt, Derya Özel, Şeyma Karagül, Ayça Tunçel, Kübra Durkan, Emin İlker Medine
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Abstract

This study presents the development and evaluation of a DFO@mAb-NP (DFO@Durvalumab-HSA-DTX nanoparticle) nanoplatform for imaging in triple-negative breast cancer (TNBC). The nanoplatform demonstrated significant changes postconjugation with DFO, evidenced by increased particle size from 178.1 ± 5 nm to 311 ± 26 nm and zeta potential alteration from −31.9 ± 3 mV to −40.5 ± 0.8 mV. Fourier-transform infrared spectroscopy and ultraviolet spectral analyses confirmed successful DFO conjugation, with notable shifts in peak wavelengths. High labeling efficiency was achieved with 89Zr, as indicated by thin layer radio chromatography and high-performance liquid radio chromatography results, with labeling efficiencies of 98 ± 2% for 89Zr-DFO@mAb and 96 ± 3% for 89Zr-DFO@mAb-NP. The nanoplatforms maintained stability over 24 h, showing less than 5% degradation. Lipophilicity assays revealed logP values of 0.5 ± 0.03 for 89Zr-DFO@mAb-NP and 0.98 ± 0.2 for 89Zr-DFO@mAb, indicating a higher lipophilic tendency in the radiolabeled Durvalumab. Cell uptake experiments showed an initial high uptake in MDA-MB-468 cells (45.1 ± 3.2%), which decreased over time, highlighting receptor-specific interactions. These comprehensive findings suggest the promising potential of the DFO@mAb-NP nanoplatform for targeted imaging in TNBC, with implications for improved diagnostic accuracy and treatment strategies.

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89Zr标记的DFO@Durvalumab-HSA纳米颗粒:体外治疗三阴性乳腺癌的潜力
本研究介绍了用于三阴性乳腺癌(TNBC)成像的 DFO@mAb-NP (DFO@Durvalumab-HSA-DTX 纳米粒子)纳米平台的开发和评估。该纳米平台在与DFO共轭后发生了显著变化,表现为粒径从178.1 ± 5 nm增至311 ± 26 nm,zeta电位从-31.9 ± 3 mV变为-40.5 ± 0.8 mV。傅立叶变换红外光谱和紫外光谱分析证实了 DFO 的成功共轭,峰值波长发生了显著变化。薄层放射色谱和高效液相放射色谱结果表明,89Zr 的标记效率很高,89Zr-DFO@mAb 的标记效率为 98 ± 2%,89Zr-DFO@mAb-NP 的标记效率为 96 ± 3%。纳米平台在 24 小时内保持稳定,降解率低于 5%。亲脂性实验显示,89Zr-DFO@mAb-NP 的 logP 值为 0.5 ± 0.03,89Zr-DFO@mAb 为 0.98 ± 0.2,这表明放射性标记的 Durvalumab 具有更高的亲脂性。细胞摄取实验显示,MDA-MB-468 细胞最初的摄取率较高(45.1 ± 3.2%),但随着时间的推移摄取率逐渐降低,这突出表明了受体特异性相互作用。这些综合研究结果表明,DFO@mAb-NP纳米平台在TNBC靶向成像方面具有广阔的潜力,对提高诊断准确性和治疗策略具有重要意义。
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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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