c-Met-Targeting 19F MRI Nanoparticles with Ultralong Tumor Retention for Precisely Detecting Small or Ill-Defined Colorectal Liver Metastases

作者：Daoshuang Li, Jie Yang, Zuoyu Xu, Yingbo Li, Yige Sun, Yuchen Wang, Hongyan Zou, Kai Wang, Lili Yang, Lina Wu, Xilin Sun · 发表于：International Journal of Nanomedicine · 年份：2023 · DOI：10.2147/ijn.s403190 · 被引用次数：10 · 研究领域：Nanoparticle-Based Drug Delivery、Liver physiology and pathology、Lanthanide and Transition Metal Complexes

Purpose: Precisely detecting colorectal liver metastases (CLMs), the leading cause of colorectal cancer-associated mortality, is extremely important. 1 H MRI with high soft tissue resolution plays a key role in the diagnosing liver lesions; however, precise detecting CLMs by 1 H MRI is a great challenge due to the limited sensitivity. Even though contrast agents may improve the sensitivity, due to their short half-life, repeated injections are required to monitor the changes of CLMs. Herein, we synthesized c-Met-targeting peptide-functionalized perfluoro-15-crown-5-ether nanoparticles (AH111972-PFCE NPs), for highly sensitive and early diagnosis of small CLMs. Methods: The size, morphology and optimal properties of the AH111972-PFCE NPs were characterized. c-Met specificity of the AH111972-PFCE NPs was validated by in vitro experiment and in vivo 19 F MRI study in the subcutaneous tumor murine model. The molecular imaging practicability and long tumor retention of the AH111972-PFCE NPs were evaluated in the liver metastases mouse model. The biocompatibility of the AH111972-PFCE NPs was assessed by toxicity study. Results: AH111972-PFCE NPs with regular shape have particle size of 89.3 ± 17.8 nm. The AH111972-PFCE NPs exhibit high specificity, strong c-Met-targeting ability, and precise detection capability of CLMs, especially small or ill-defined fused metastases in 1 H MRI. Moreover, AH111972-PFCE NPs could be ultralong retained in metastatic liver tumors for at least 7 days...