Triple-negative breast cancer (TNBC) presents significant challenges due to its aggressive behavior and lack of targeted treatments. High-resolution imaging techniques and targeted nanoparticles offer potential solutions for early detection and monitoring of TNBC. In this study, we developed and characterized solid lipid nanoparticles (SLNs) conjugated with a C-peptide derived from endostatin to target integrin αvβ₃, overexpressed in TNBC. These SLNs were loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for enhanced magnetic resonance imaging (MRI) and radiolabeled with technetium-99m (^99mTc) for single-photon emission computed tomography (SPECT), enabling dual-modality imaging. Extensive characterization of the nanoparticles was performed utilizing a variety of advanced techniques, including dynamic light scattering (DLS), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), field-emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM). This comprehensive analysis validated the successful synthesis and functionalization of the nanoparticles, along with their remarkable magnetic properties, while also revealing their distinct spherical morphology, optimal size, uniform distribution, and colloidal stability. The conjugation of C-peptide significantly enhanced the targeting efficiency in vitro, as evidenced by the MTT and receptor-binding assays in 4T1 cells using flow cytometry and MRI. In vivo studies using a 4T1 murine model demonstrated that peptide-conjugated SLNs accumulated in tumor tissues, providing superior contrast in MRI and enhanced tumor-specific localization in SPECT imaging. Biodistribution analysis confirmed reduced off-target accumulation, particularly in the liver, compared to nontargeted formulations. Collectively, C-peptide-conjugated SLNs provide a promising dual-modality imaging platform for TNBC, offering improved diagnostic accuracy and tumor targeting.

© 2025 The Authors. Published by American Chemical Society.

三阴性乳腺癌（TNBC）因其侵略性和缺乏靶向治疗而带来了重大挑战。高分辨率成像技术和靶向纳米颗粒为早期检测和监测 TNBC 提供了潜在的解决方案。在这项研究中，我们开发并表征了一种与源自端粒酶抑制剂的 C 肽结合的固体脂质纳米颗粒（SLNs），该肽针对在 TNBC 中过表达的整合素 αvβ3。这些 SLNs 装载有超顺磁性铁氧体纳米颗粒（SPIONs）以增强磁共振成像（MRI），并用锝-99m (^99mTc) 放射标记，用于单光子发射计算机断层扫描（SPECT），从而实现双模态成像。利用动态光散射（DLS）、差示扫描量热法（DSC）、热重分析（TGA）、X 射线衍射（XRD）、振动样品磁强计（VSM）、场发射扫描电子显微镜（FE-SEM）和原子力显微镜（AFM）等先进技术对纳米颗粒进行了详细的表征。这项综合分析验证了成功合成并功能化后的纳米颗粒，同时揭示了它们出色的磁性属性、独特的球形形态、最佳尺寸、均匀分布以及胶体稳定性。C 肽结合显著提高了靶向效率，如 MTT 和受体结合试验在 4T1 细胞中使用流式细胞术和 MRI 所示的体内研究结果表明，肽结合 SLNs 在肿瘤组织中的积累情况良好，为 MRI 提供了更好的对比度，并且在 SPECT 成像中实现了增强的肿瘤特异性定位。生物分布分析证实与非靶向配方相比，在肝脏等部位的脱靶积聚减少。总的来说，C 肽结合的 SLNs 为 TNBC 提供了一种有前景的双模态成像平台，提高了诊断准确性及肿瘤靶向性。

© 2025 The Authors. Published by American Chemical Society.