Liposomal MRI probes containing encapsulated or amphiphilic Fe(III) coordination complexes
Liposomal MRI probes containing encapsulated or amphiphilic Fe(III) coordination complexes
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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
DOI：
10.1039/d3bm00029j
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发表时间：
2023
影响因子：
6.6
通讯作者：
Morrow, Janet R.
中科院分区：
文献类型：
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作者：
Chowdhury, Md Saiful;Kras, Elizabeth A.;Turowski, Steven G.;Spernyak, Joseph A.;Morrow, Janet R.
制备含有高自旋Fe（III）配位络合物的脂质体，以生产具有改善的弛豫率的T1 MRI探针。两亲性Fe（III）配合物锚定到脂质体中，具有两个烷基链，得到含有混合酰胺和羟丙基侧基的配位球。包封的配合物含有一个大环配体，带有三个膦酸酯侧基[Fe（NOTP）]3−，选择它是因为它具有良好的水溶性。制备了四种类型的MRI探针，包括单独的脂质体内Fe（III）络合物（LipoA）、两亲性Fe（III）络合物（LipoB）、脂质体内和两亲性络合物（LipoC）以及由两亲性络合物形成的胶束。水质子弛豫率R1和R2进行了测量，并与含有类似供体基团的小分子大环Fe（III）配合物进行了比较。两亲性Fe（III）络合物的胶束的质子弛豫率值（r1 = 2.6 mM−1 s−1）是小亲水性类似物的四倍。具有两亲性Fe（III）络合物的脂质体（LipoB）在pH 7.2、34 °C和1.4 T下的每铁弛豫率为2.6 mM−1 s−1，而含有两亲性和脂质体内Fe（III）络合物的脂质体（lipoC）在每铁基础上的r1为0.58 mM−1 s−1，这与内部Fe（III）络合物弛豫率的淬灭一致。仅含有包封的[Fe（NOTP）]3−的脂质体具有降低的r1，每个铁络合物为0.65 mM−1 s−1。研究表明，不同类型的脂质体纳米粒的体内分布和清除率有很大差异。LipoB是具有长循环时间的血池剂，而lipoC通过肾脏和肝胆途径更快地清除。这些清除率差异与LipoC的稳定性低于LipoB一致。
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.