Novel Nanoprobe with Combined Ultrasonography/Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Precise Diagnosis of Tumors

Jieqiong Ding; Liu He; Lin Yang; Liyuan Cheng; Zhiwei Zhao; Binhua Luo; Yanlong Jia

doi:10.3390/pharmaceutics15122693

Novel Nanoprobe with Combined Ultrasonography/Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Precise Diagnosis of Tumors

Pharmaceutics. 2023 Nov 28;15(12):2693. doi: 10.3390/pharmaceutics15122693.

Authors

Jieqiong Ding¹, Liu He¹, Lin Yang², Liyuan Cheng¹, Zhiwei Zhao³, Binhua Luo¹, Yanlong Jia⁴

Affiliations

¹ Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
² Department of Radiology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China.
³ Department of Radiology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China.
⁴ Department of Radiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China.

Abstract

Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient's results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and -39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.

Keywords: CEST MR imaging; PEG-PLLA; US imaging; nanoparticle; nanoprobe.

Grants and funding

This work was supported by the Hubei Provincial Natural Science Foundation of China (grant no. 2022CFB960); Scientific research and development funds of Hubei University of Science and Technology (grant no. 2022-24GP01); and Xiangyang City Science and Technology Program in Health Care (2022YL15A).