Samari Melika, Alamzadeh Zahra, Irajirad Rasoul, Sarikhani Abolfazl, Mahabadi Vahid Pirhajati, Ghaznavi Habib, Khoei Samideh
Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran.
Medical Physics Department, Iran University of Medical Sciences, Tehran, Iran.
BMC Biomed Eng. 2025 May 1;7(1):5. doi: 10.1186/s42490-025-00091-7.
The aim of this study was to produce ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) conjugated to the FROP-1 peptide for targeted magnetic resonance imaging (MRI) of breast cancer cell lines and to evaluate its application as a specific and targeted T1-weighted MR imaging contrast agent in vitro. Sodium citrate-stabilized FeO NPs were conjugated with the FROP-1 peptide by 1-ethyl-3-(3-dimethylaminopropyl) carbide diamide hydrochloride (EDC) to form a novel FeO@FROP-1 specific target contrast agent. The specificity and targeting of FeO@FROP-1 to bind FROP-1 receptors were investigated in vitro by cellular uptake and cellular MR imaging.
In this study, the synthesis of water-soluble ultrasmall FeO NPs was performed by the co-precipitation method. XRD, TEM, and VSM analyses showed the formation of the FeO NPs with an average size of about 3.78 ± 0.2 nm. FT-IR spectroscopy approved the conjugation of the FROP-1 peptide with the FeO NPs. The synthesized FeO@FROP-1 NPs showed good biocompatibility, and the high r1 relaxivity and r2/r1, respectively, were 2.608 mMS and 1.18. The biocompatibility of the FeO and FeO@FROP-1 NPs on the MCF-7, SKBR-3, MDA-MB-231, and MCF-10 cell lines was determined using cytotoxicity analysis. The specific targeting effect on the cells was verified by in vitro cellular uptake and cell MR imaging.
It was found that the contrast intensity of the FeO@FROP-1 nanoprobe increases as Fe concentration increases. Cellular uptake of the FeO and FeO@FROP-1 NPs was quantified using ICP-MS. The synthesized NPs had better imaging performance than Dotarem (gadoterate meglumine). The findings showed that FeO@FROP-1 NPs have potential utility as a specific and targeted T1-weighted contrast agent in breast cancer MR imaging.
本研究的目的是制备与FROP-1肽偶联的超小超顺磁性氧化铁（USPIO）纳米颗粒（NPs），用于乳腺癌细胞系的靶向磁共振成像（MRI），并在体外评估其作为特异性靶向T1加权磁共振成像造影剂的应用。通过1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐（EDC）将柠檬酸钠稳定的FeO NPs与FROP-1肽偶联，形成新型的FeO@FROP-1特异性靶向造影剂。通过细胞摄取和细胞磁共振成像在体外研究了FeO@FROP-1与FROP-1受体结合的特异性和靶向性。
在本研究中，采用共沉淀法合成了水溶性超小FeO NPs。X射线衍射（XRD）、透射电子显微镜（TEM）和振动样品磁强计（VSM）分析表明，形成了平均尺寸约为3.78±0.2 nm的FeO NPs。傅里叶变换红外光谱（FT-IR）证实了FROP-1肽与FeO NPs的偶联。合成的FeO@FROP-1 NPs表现出良好的生物相容性，其高r1弛豫率和r2/r1分别为2.608 m M⁻¹s⁻¹和1.18。使用细胞毒性分析确定了FeO和FeO@FROP-1 NPs对MCF-7、SKBR-3、MDA-MB-231和MCF-10细胞系的生物相容性。通过体外细胞摄取和细胞磁共振成像验证了对细胞的特异性靶向作用。
发现FeO@FROP-1纳米探针的对比强度随铁浓度的增加而增加。使用电感耦合等离子体质谱（ICP-MS）对FeO和FeO@FROP-1 NPs的细胞摄取进行了定量。合成的NPs具有比多他胺（钆喷酸葡胺）更好的成像性能。研究结果表明，FeO@FROP-1 NPs在乳腺癌磁共振成像中作为特异性靶向T1加权造影剂具有潜在应用价值。
