含有封装或两亲性 Fe(III) 配位络合物的脂质体 MRI 探针,Biomaterials Science

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含有封装或两亲性 Fe(III) 配位络合物的脂质体 MRI 探针
Biomaterials Science ( IF 5.8 ) Pub Date : 2023-07-14 , DOI: 10.1039/d3bm00029j
Md Saiful I Chowdhury ₁ , Elizabeth A Kras ₁ , Steven G Turowski ₂ , Joseph A Spernyak ₂ , Janet R Morrow ₁

Affiliation

制备含有高自旋 Fe( III ) 配位络合物的脂质体，用于生产具有改善弛豫性的T _{1 MRI 探针。}两亲性 Fe( III ) 配合物通过两条烷基链锚定到脂质体中，形成含有混合酰胺和羟丙基侧基的配位球。封装的复合物包含具有三个膦酸酯侧链的大环配体，[Fe(NOTP)] ³⁻，因其良好的水溶性而被选择。制备了四种类型的MRI探针，包括单独具有脂质体内Fe( III )复合物(LipoA)、两亲性Fe( III )复合物(LipoB)、脂质体内和两性复合物(LipoC)或由两性复合物形成胶束的探针。测量了水质子弛豫率r ₁和r ₂ ，并与含有相似供体基团的小分子大环Fe( III )络合物进行比较。两亲性Fe( III )络合物的胶束的质子弛豫率值( r ₁ = 2.6 mM ^-1 s ^-1 )比小的亲水类似物高四倍。具有两亲性 Fe( III ) 络合物 (LipoB) 的脂质体在 pH 7.2、34 °C、1.4 T 下的每铁弛豫率为 2.6 mM ^-1 s ^-1 ，而同时含有两亲性和脂质体内 Fe( III ) 络合物 (lipoC) 的脂质体具有r ₁为0.58 mM ^-1 s ^-1 (以每铁计)，与内部Fe( III )络合物弛豫率的淬灭一致。仅包含封装的[Fe(NOTP)] ³⁻的脂质体具有每个铁络合物0.65 mM ^-1 s ^-1的降低的r _{1 。}研究表明，不同类型的脂质体纳米颗粒的生物分布和清除率差异很大。LipoB 是一种循环时间较长的血池剂，而 lipoC 通过肾脏和肝胆途径清除得更快。这些清除率差异与 LipoC 相比 LipoB 稳定性较低的情况一致。

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Liposomal MRI probes containing encapsulated or amphiphilic Fe(III) coordination complexes

Liposomes containing high-spin Fe(III) coordination complexes were prepared towards the production of T₁ MRI probes with improved relaxivity. The amphiphilic Fe(III) complexes were anchored into the liposome with two alkyl chains to give a coordination sphere containing mixed amide and hydroxypropyl pendant groups. The encapsulated complex contains a macrocyclic ligand with three phosphonate pendants, [Fe(NOTP)]³⁻, which was chosen for its good aqueous solubility. Four types of MRI probes were prepared including those with intraliposomal Fe(III) complex (LipoA) alone, amphiphilic Fe(III) complex (LipoB), both intraliposomal and amphiphilic complex (LipoC) or micelles formed with amphiphilic complex. Water proton relaxivities r₁ and r₂ were measured and compared to a small molecule macrocyclic Fe(III) complex containing similar donor groups. Micelles of the amphiphilic Fe(III) complex had proton relaxivity values (r₁ = 2.6 mM⁻¹ s⁻¹) that were four times higher than the small hydrophilic analog. Liposomes with amphiphilic Fe(III) complex (LipoB) have a per iron relaxivity of 2.6 mM⁻¹ s⁻¹ at pH 7.2, 34 °C at 1.4 T whereas liposomes containing both amphiphilic and intraliposomal Fe(III) complexes (lipoC) have r₁ of 0.58 mM⁻¹ s⁻¹ on a per iron basis consistent with quenching of the interior Fe(III) complex relaxivity. Liposomes containing only encapsulated [Fe(NOTP)]³⁻ have a lowered r₁ of 0.65 mM⁻¹ s⁻¹ per iron complex. Studies show that the biodistribution and clearance of the different types liposomal nanoparticles differ greatly. LipoB is a blood pool agent with a long circulation time whereas lipoC is cleared more rapidly through both renal and hepatobiliary pathways. These clearance differences are consistent with lower stability of LipoC compared to LipoB.

更新日期：2023-07-14

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