Multifunctional Theranostic Nanoparticles Based on Exceedingly Small Magnetic Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging and Chemotherapy

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Abstract
The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) (T1-weighted contrast agents for magnetic resonance imaging (MRI) due to their good biocompatibility compared with Gd-chelates. However, the best particle size of ES-MIONs for T1 imaging is still unknown because the synthesis of ES-MIONs with precise size control to clarify the relationship between the r1 (or r2/r1) and the particle size remains a challenge. In this study, we synthesized ES-MIONs with seven different sizes below 5 nm and found that 3.6 nm is the best particle size for ES-MIONs to be utilized as T1-weighted MR contrast agent. To enhance tumor targetability of theranostic nanoparticles and reduce the nonspecific uptake of nanoparticles by normal healthy cells, we constructed a drug delivery system based on the 3.6 nm ES-MIONs for T1-weighted tumor imaging and chemotherapy. The laser scanning confocal microscopy (LSCM) and flow cytometry analysis results demonstrate that our strategy of precise targeting via exposure or hiding of the targeting ligand RGD2 on demand is feasible. The MR imaging and chemotherapy results on the cancer cells and tumor-bearing mice reinforce that our DOX@ES-MION3@RGD2@mPEG3 nanoparticles are promising for high-resolution T1-weighted MR imaging and precise chemotherapy of tumors.
Funding Information
  • Ministry of Science and Technology of the People's Republic of China (2016YFC1400600)
  • Ningbo Municipal Bureau of Science and Technology (2015B11002)
  • National Institute of Biomedical Imaging and Bioengineering (ZIA EB000073)
  • Youth Innovation Promotion Association of the Chinese Academy of Sciences (2016269)
  • National Natural Science Foundation of China (21305148, 51761145021, 61571278)
  • Zhejiang Province (2017C33129)

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