Liposomal Fe(III) Macrocyclic Complexes with Hydroxypropyl Pendants as MRI Probes.
Liposomal Fe(III) Macrocyclic Complexes with Hydroxypropyl Pendants as MRI Probes.
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DOI：
10.1021/acsabm.1c00879
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发表时间：
2021-11-15
影响因子：
4.7
通讯作者：
Morrow, Janet R
中科院分区：
文献类型：
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作者：
Abozeid, Samira M;Chowdhury, Md Saiful I;Asik, Didar;Spernyak, Joseph A;Morrow, Janet R
以含2-羟丙基的1，4，7-三氮杂环大环的单核(Fe(L1)或Fe(L3))或双核(Fe2(L2))配合物为载体，制备了含Fe(III)配合物的顺磁性脂质体。制备了两种不同类型的顺磁性脂质体。第一种类型是LipoA，将单核Fe(L1)络合物加载到内部水核中。第二种类型是LipoB，将两亲性Fe(L3)络合物插入到脂质体双层和内部水核中，负载Fe(L1)(LipoB1)或Fe2(L2)(LipoB2)。LipoA可提高T1和T2的水质子弛豫速率。用渗透压梯度处理LipoA以产生非球形脂质体，产生具有化学交换饱和转移(CEST)效应的脂质体，如不对称分析所示，但仅在高渗透压下。脂质体双层中含有两亲性复合体的LipoB1在用渗透压梯度处理脂质体时产生了加宽的Z-谱。LipoB1和LipoB2的R1弛豫度均高于LipoA的R1弛豫度，表明两亲Fe(III)中心的贡献较大。在一定的磁场强度范围内(1.4T~9.4T)，顺磁性脂质体的R_1驰豫系数相对恒定，且R_2/R_1比值在高场强下显著增加。小鼠体内LipoB1的MRI研究显示，与临床使用的Gd(DOTA)相比，LipoB1在血液中的对比增强时间更长，Gd(DOTA)的每金属注射剂量比负载Fe(III)的脂质体高2倍。
Paramagnetic liposomes containing Fe(III) complexes were prepared by incorporation of mononuclear (Fe(L1) or Fe(L3)) or dinuclear (Fe2(L2)) coordination complexes of 1,4,7-triazacyclononane macrocycles containing 2-hydroxypropyl pendant groups. Two different types of paramagnetic liposomes were prepared. The first type, LipoA, has the mononuclear Fe(L1) complex loaded into the internal aqueous core. The second type, LipoB, has the amphiphilic Fe(L3) complex inserted into the liposomal bilayer and the internal aqueous core loaded with either Fe(L1) (LipoB1), or Fe2(L2) (LipoB2). LipoA enhances both T1 and T2 water proton relaxation rates. Treatment of LipoA with osmotic gradients to produce a non-spherical liposome produces a liposome with a chemical exchange saturation transfer (CEST) effect as shown by an asymmetry analysis, but only at high osmolarity. LipoB1, which contains an amphiphilic complex in the liposomal bilayer produced a broadened Z-spectrum upon treatment of the liposome with osmotic gradients. The r1 relaxivity of LipoB1 and LipoB2 were higher than the r1 relaxivity of LipoA on a per Fe basis, suggesting an important contribution from the amphiphilic Fe(III) center. The r1 relaxivities of paramagnetic liposomes are relatively constant over a range of magnetic field strengths (1.4 T to 9.4 T), with the ratio of r2/r1 substantially increasing at high field strength. MRI studies of LipoB1 in mice showed prolonged contrast enhancement in blood compared to the clinically employed Gd(DOTA), which was injected at 2-fold higher dose per metal than the Fe(III) loaded liposomes.