Synthesis and in vitro evaluation of manganese(II)-porphyrin modified with chitosan oligosaccharides as potential MRI contrast agents

Abstract

Mn-TCPP-CS _n(n=6, 11, 20) as a type of potential magnetic resonance imaging(MRI) contrast agents were synthesized via manganese(II) meso-tetra(4-carboxyphenyl) porphyrin(Mn-TCPP) modified with chitosan oligosaccharides(CS _n). Experimental data of infared(IR), UV-Vis, MS, inductively coupled plasma-atomic emission spectrometer(ICP-AES) and size exclusion chromatography evidenced the formation of Mn-TCPP-CS _n. The stability results show that Mn-TCPP-CS _n in aqueous solution was stable enough to prevent Mn(II) ions from leaking. The magnetic properties in vitro indicate that Mn-TCPP-CS₂₀ possesses higher longitudinal relaxivity(r ₁=10.38 L·mmol⁻¹·s⁻¹) in aqueous solution than unmodified porphyrin Mn-TCPPNa₄[manganese(II) meso-tetra(4-carboxyphenyl) porphyrin, tetrasodium salt](r ₁=5.10 L·mmol⁻¹·s⁻¹) and the commercial contrast agent Gd-DTPA(r ₁=4.05 L·mmol⁻¹·s⁻¹). The preliminary T ₁-weighted flash image studies in vitro show that the contrast and the imaging signal of Mn-TCPP-CS _n were superior to those of Mn-TCPPNa4 and Gd-DTPA under the same conditions. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay shows that Mn-TCPP-CS _n has a good biocompatibility. In addition, the thermodynamical parameters(ΔH<0, ΔS<0, ΔG<0) of Mn-TCPP-CS _n bound to bovine serum albumin(BSA) show that Mn-TCPP-CS _n could bind to BSA spontaneously, where the binding complex was stabilized mainly by van der Waals interactions and hydrogen bonds. These results suggest that Mn-TCPP-CS _n have the advantage of becoming a potential MRI contrast agent.

Keywords

MRI contrast agent / Porphyrin / Chitosan oligosaccharide / Relaxivity / T ₁-Weighted flash image

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