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PDGF-B conjugating mesoporous IO/GdO nanocomposites for accurate diagnosis of orthotopic prostatic cancer through T1-T2 dual-modal MRI contrast enhancement

Journal 2022 · IF 9.918 · 发表于 2022 年 8 月 26 日
作者: Qingdong Li,Jianmin Xiao,Caiyun Zhang,Peng Wang,Wenling Li,Yinfeng Wang,Lang Ran,Xia Qin,Miao Yan,Junchao Qian,Zhengyan Wu,Geng Tian,Pengfei Wei,Guilong Zhang
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摘要

The development of highly efficient magnetic resonance imaging (MRI) contrast agent contributes to the early and accurate diagnosis of cancer. Herein, we developed a novel iron oxide and gadolinium oxide (IO/GdO) nanocomposite as T 1 -T 2 dual modal MRI contrast agent through hydrothermal synthesis method. Subsequently, tumor-targeting ligand (PDGFB-PEG) was further conjugated to the surface of IO/GdO nanocomposite (PDGFB-pIO/GdO) to fabricate tumor-targeting MRI probe for accurate diagnosis of orthotopic prostatic cancer. IO/GdO nanocomposite exhibited obvious mesoporous structure, which would promote the contact between water molecules and Gd or Fe centers and enhance the T 1 relaxation rate (r 1 ) and T 2 relaxation rate (r 2 ) of IO/GdO composite. In addition, the r 1 and r 2 values of IO/GdO composite were up to be 11.6 mM −1 s −1 and 102.7 mM −1 s −1 , respectively, and the r 2 /r 1 ratio of IO/GdO nanocomposite was calculated to be 8.85, demonstrating a great potential as dual-mode MRI contrast agent. Further study indicated that PDGFB-pIO/GdO exhibited an excellent biocompatibility. Besides, PDGFB-pIO/GdO presented a higher accumulation in tumor than untargeted pIO/GdO, confirming its excellent in vivo tumor-targeting ability. Lastly, in orthotopic prostatic cancer model, the systemic delivery of PDGFB-pIO/GdO significantly enhanced T 1 - and T 2 -weighted signal of orthotopic prostatic cancer, achieving high quality of MR images and realizing accurate diagnosis of orthotopic prostatic cancer. Collectively, we proposed a rational designed nanoplatform, PDGF-B conjugating mesoporous IO/GdO nanocomposites, suggesting potential for diagnostic identification of prostate cancer via T 1 -T 2 dual-modal MRI contrast enhancement.