由高密度 Gd-DTPA-双（硬脂酰胺）实现的延长循环脂质纳米颗粒用于持久增强的肿瘤磁共振成像,Bioconjugate Chemistry

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由高密度 Gd-DTPA-双（硬脂酰胺）实现的延长循环脂质纳米颗粒用于持久增强的肿瘤磁共振成像
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2022-10-28 , DOI: 10.1021/acs.bioconjchem.2c00445
Denis A Margalik _{1,

2} , Juan Chen ₁ , Tiffany Ho _{1,

3} , Lili Ding ₁ , Alexander Dhaliwal _{1,

4} , Andrea S Doria ₅ , Gang Zheng _{1,

2,

3,

4}

Affiliation

卟啉体 (PS) 被探索将不同类型的二亚乙基三胺五乙酸-钆-(III) (Gd-DTPA)-脂质掺入其双层膜中，以评估 PS 作为 MRI 造影剂的潜力。Gd-dPS-BSA 通过在 PS 构建中整合超过 30% 的 Gd-DTPA-双（硬脂酰胺）(Gd-DTPA-BSA)-脂质，导致异常的血清稳定性和 13 mM –1 的 T 1和^T₂弛豫_测量s ^–1和 19 mM ^–1 s ^–1，分别。在选定的癌症小鼠模型中，Gd-dPS-BSA 在注射后 72 小时表现出显着增强的血液循环保留，半衰期为 13.6 小时，肿瘤积累高达 19.5%ID/g。此外，Gd-dPS-BSA 在 24、48 和 72 小时内显示出出色的 MRI 肿瘤增强，对比增强分别比基线高 35.8%、38.2% 和 38.3%。此处报告的结果强调了 Gd-DTPA-BSA-脂质在 PS 中的高密度掺入，而其他脂质体制剂可以延长循环寿命，与颗粒浓度无关，表明 Gd-dPS-BSA 的有效 MRI 造影剂潜力和潜在效用Gd-DTPA-BSA-脂质以增强其他脂质体影响的诊断和治疗功能。

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Prolonged Circulating Lipid Nanoparticles Enabled by High-Density Gd-DTPA-Bis(stearylamide) for Long-Lasting Enhanced Tumor Magnetic Resonance Imaging

Porphysomes (PS) were explored to incorporate different types of diethylenetriaminepentaacetic-acid-gadolinium-(III) (Gd-DTPA)-lipids into their bilayer membrane to assess PS potential as an MRI contrast agent. The Gd-dPS-BSA by integration of over 30% Gd-DTPA-bis(stearylamide) (Gd-DTPA-BSA)-lipids in PS construction resulted in exceptional serum stability and T₁ and T₂ relaxivity measurements of 13 mM^–1 s^–1 and 19 mM^–1 s^–1, respectively. The Gd-dPS-BSA demonstrated significantly enhanced retention in blood circulation with a half-life of 13.6 h and high tumor accumulation up to 19.5%ID/g at 72 h post-injection in select cancer mouse models. Additionally, Gd-dPS-BSA displayed excellent MRI tumor enhancement over 24, 48, and 72 h with contrast enhancements from the baseline of 35.8%, 38.2%, and 38.3%, respectively. Results reported here highlight a high-density incorporation of Gd-DTPA-BSA-lipids within PS, and other liposome formulations can enhance circulatory longevity, independently of particles’ concentration, suggesting effective MRI contrast agent potential for Gd-dPS-BSA and potential utility of Gd-DTPA-BSA-lipids to enhance other liposomal-influenced diagnostic and therapeutic functions.

更新日期：2022-10-28

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