Preparation of Mn²⁺@PolyDOPA-b-polysarcosine micelle as MRI contrast agent with high longitudinal relaxivity

Abstract

Magnetic resonance imaging (MRI) is a promising technique widely used in clinical diagnose. Poly(α-amino acid)s are excellent carriers for MRI due to their excellent biocompatibility. PDOPA-b-PSar copolymers (defined as “DoS”) are synthesized by sequential polymerizations of 3,4-dihydroxy-L-phenylalanine N-thiocarboxyanhydride (DOPA-NTA) and sarcosine N-thiocarboxyanhydride (Sar-NTA) initiated by neopentylamine in tetramethylene sulfone. Mn²⁺@DoS micelles have been prepared as T₁-weighted MRI contrast agents according to efficient coordination between catechol units and Mn²⁺ cation. High longitudinal relaxivity (27.7 mM⁻¹·s⁻¹) of Mn²⁺@PDOPA₁₂-b-PSar₇₂ was observed, and the aqueous micelle exhibits effective MRI contrast enhancement in vivo of nude mice. Mn²⁺@DoS shows potential clinical application in diagnostic radiology as a novel MRI contrast agent. Gd³⁺@DoS micelles are also investigated presenting a longitudinal relaxivity of 16.4 mM⁻¹·s⁻¹. Unfortunately, the Gd³⁺ loading percentage is quite low as 19%.

Keywords:

• Poly(α-amino acid)s
• polypeptides
• polypeptoids
• magnetic resonance imaging
• longitudinal relaxivity

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This study was supported by the National Key Research and Development Program of China (2016YFA0100900), the National Natural Science Foundation of China (21674091, 81871403, 61976075), Key Research and Development Program of Zhejiang Province (2019C03014), Joint Foundation of Shaanxi Province Natural Science Basic Research Program and Shaanxi Coal Chemical Group Co., Ltd. (2019JLM-46), and Zhejiang basic public welfare research program (LGF18H180009).