Stem cell–nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy

Yen-Ho Lai, Chia-Yu Su, Hung-Wei Cheng, Chao-Yi Chu, Long-Bin Jeng, Chih-Sheng Chiang (), Woei-Cherng Shyu () and San-Yuan Chen ()
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Yen-Ho Lai: China Medical University Hospital
Chia-Yu Su: Taipei Medical University
Hung-Wei Cheng: National Yang Ming Chiao Tung University
Chao-Yi Chu: National Yang Ming Chiao Tung University
Long-Bin Jeng: China Medical University Hospital
Chih-Sheng Chiang: China Medical University Hospital
Woei-Cherng Shyu: China Medical University
San-Yuan Chen: National Yang Ming Chiao Tung University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The potential clinical application of gadolinium-neutron capture therapy (Gd-NCT) for glioblastoma multiforme (GBM) treatment has been compromised by the fast clearance and nonspecific biodistribution of gadolinium-based agents. We have developed a stem cell–nanoparticle system (SNS) to actively target GBM for advanced Gd-NCT by magnetizing umbilical cord mesenchymal stem cells (UMSCs) using gadodiamide-concealed magnetic nanoparticles (Gd-FPFNP). Nanoformulated gadodiamide shielded by a dense surface composed of fucoidan and polyvinyl alcohol demonstrates enhanced cellular association and biocompatibility in UMSCs. The SNS preserves the ability of UMSCs to actively penetrate the blood brain barrier and home to GBM and, when magnetically navigates by an external magnetic field, an 8-fold increase in tumor-to-blood ratio is achieved compared with clinical data. In an orthotopic GBM-bearing rat model, using a single dose of irradiation and an ultra-low gadolinium dose (200 μg kg−1), SNS significantly attenuates GBM progression without inducing safety issues, prolonging median survival 2.5-fold compared to free gadodiamide. The SNS is a cell-based delivery system that integrates the strengths of cell therapy and nanotechnology, which provides an alternative strategy for the treatment of brain diseases.

Date: 2023
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DOI: 10.1038/s41467-023-35935-0

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