Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability

Shi Bai; Xiao-Dan Zhang; Yu-Qi Zou; Yu-Xi Lin; Zhi-Yao Liu; Ke-Wen Li; Ping Huang; Takashi Yoshida; Yi-Li Liu; Ming-Shan Li; Wei Zhang; Xiao-Ju Wang; Min Zhang; Cheng Du

doi:10.3389/fbioe.2024.1382085

Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability

Front Bioeng Biotechnol. 2024 Mar 20:12:1382085. doi: 10.3389/fbioe.2024.1382085. eCollection 2024.

Authors

Shi Bai¹, Xiao-Dan Zhang¹, Yu-Qi Zou¹, Yu-Xi Lin¹, Zhi-Yao Liu¹, Ke-Wen Li¹, Ping Huang¹, Takashi Yoshida², Yi-Li Liu³, Ming-Shan Li³, Wei Zhang⁴, Xiao-Ju Wang⁵, Min Zhang⁶, Cheng Du⁴

Affiliations

¹ Department of Information Engineering, Shenyang University of Technology, Shenyang, China.
² Department of Electrical Engineering, Kyushu University, Fukuoka, Japan.
³ Department of Urology, Fourth Affiliated Hospital of China Medical University, Shenyang, China.
⁴ Department of Oncology, General Hospital of Northern Theater Command, Shenyang, China.
⁵ Department of Foreign Languages, Liaoning Vocational and Technical College of Economics, Shenyang, China.
⁶ First Affiliated Hospital, China Medical University, Shenyang, China.

Abstract

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Keywords: drug delivery; magnetic drug targeting; magnetic particle imaging; superparamagnetic iron oxide nanoparticles; tumor therapy.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This paper was supported in part by the National Natural Science Foundation of China (Grant Number 62001313), the Liaoning Provincial Natural Science Foundation of China (Grant Number 2020-MS-211, 2022-YGJC-11, 2022-YGJC-29, 2022-YGJC-35), the Key Project of Liaoning Provincial Department of Education (Grant Number LJKZ0133), and the Key Project of Liaoning Provincial Department of Science and Technology (Grant Number 2021JH2/10300134), Science and Technology Project of Shenyang City (Grant No. 22-321-32-09).