Synthesis and in vitro Evaluation of Manganese（Ⅱ）-porphyrin Modified with Chitosan Oligosaccharides as Potential MRI Contrast Agents

Mn-TCPP-CSn（n=6,1 1,20） 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（CSn）.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-CSn-The stability results show that Mn-TCPP-CSn 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（r1=10.38 L·mmol^-1·s^-1） in aqueous solution than unmodified porphyrin Mn-TCPPNa4[manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin,tetrasodium salt]（r1=5.10 L·mmol^-1·s^-1） and the commercial contrast agent Gd-DTPA（r1=4.05 L·mmol^-1·s^-1）.The preliminary T1-weighted flash image studies in vitro show that the contrast and the imaging signal of Mn-TCPP-CSn 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-CSn has a good biocompatibility.In addition,the thermodynamical parameters（ΔH〈0,ΔS〈0,ΔG〈0） of Mn-TCPP-CSn bound to bovine serum albumin（BSA） show that Mn-TCPP-CSn 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-CSn have the advantage of becoming a potential MRI contrast agent.

Synthesis and in vitro Evaluation of Manganese(II)-porphyrin Modified with Chitosan Oligosaccharides as Potential MRI Contrast Agents

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(r₁=10.38 L·mmol^-1·s^-1) in aqueous solution than unmodified porphyrin Mn-TCPPNa₄[manganese(II) meso-tetra(4-carboxyphenyl) porphyrin, tetrasodium salt](r₁=5.10 L·mmol^-1·s^-1) and the commercial contrast agent Gd-DTPA(r₁=4.05 L·mmol^-1·s^-1). The preliminary T₁-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.