Princess Margaret Cancer Centre, University Health Network 101 College St., PMCRT 5-354, Toronto, ON M5G 1L7, Canada.
Institute of Biomedical Engineering, University of Toronto 64 College St., Toronto, ON M5S 3G9, Canada.
Bioconjug Chem. 2022 Nov 16;33(11):2213-2222. doi: 10.1021/acs.bioconjchem.2c00445. Epub 2022 Oct 28.
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 T and T relaxivity measurements of 13 mM s and 19 mM s, 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.
血影蛋白（PS）被探索用于将不同类型的二亚乙基三胺五乙酸-钆（III）（Gd-DTPA）-脂质整合到双层膜中，以评估 PS 作为 MRI 造影剂的潜力。通过将超过 30%的 Gd-DTPA-双（硬脂酰胺）（Gd-DTPA-BSA）-脂质整合到 PS 构建中，得到了 Gd-dPS-BSA，其血清稳定性和 T1 和 T2弛豫率分别为 13 mM s 和 19 mM s。Gd-dPS-BSA 表现出明显增强的血液循环保留，半衰期为 13.6 h，在注射后 72 h 在选定的癌症小鼠模型中达到高达 19.5%ID/g 的肿瘤积累。此外，Gd-dPS-BSA 在 24、48 和 72 h 时显示出出色的 MRI 肿瘤增强，与基线相比增强分别为 35.8%、38.2%和 38.3%。这里报道的结果突出了 Gd-DTPA-BSA-脂质在 PS 中的高密度掺入，并且其他脂质体制剂可以独立于颗粒浓度延长循环寿命，这表明 Gd-dPS-BSA 具有有效的 MRI 造影剂潜力，并且 Gd-DTPA-BSA-脂质具有增强其他脂质体影响的诊断和治疗功能的潜力。
