Rapid and continuous accumulation of nitric oxide-releasing liposomes in tumors to augment the enhanced permeability and retention (EPR) effect
Rapid and continuous accumulation of nitric oxide-releasing liposomes in tumors to augment the enhanced permeability and retention (EPR) effect
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DOI：
10.1016/j.ijpharm.2019.05.043
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发表时间：
2019-06-30
影响因子：
5.8
通讯作者：
Katayama, Yoshiki
中科院分区：
文献类型：
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作者：
Yoshikawa, Takuma;Mori, Yukina;Katayama, Yoshiki
调节肿瘤的血流是改善纳米药物在肿瘤中积聚的一种重要策略，这是由于渗透性和保留性增强（EPR）效应造成的。我们以前报道了一种有前途的EPR增强剂-一氧化氮（NO）供体含有脂质体（NO-LP）-这表明在肿瘤组织中的积累增强。在此，我们更详细地研究了NO-LP，以阐明其作为EPR增强剂的实际用途。NO-LP被认为具有优势，作为一个NO供体，包括能够维持NO捐赠在很长一段时间内，和一个恒定的NO释放速率，而不管环境pH值。NO-LP注射后（1小时），在肿瘤组织中迅速积累，然后积累不断增强，直到48小时。NO-LP在肿瘤中的蓄积明显增强，而在其他器官中的蓄积相对不变。所获得的结果显示了NO-LP作为EPR增强剂的有前途的功能。
The modulation of blood flow to tumors is a prominent strategy for improving the tumor accumulation of nanomedicines, resulting from the enhanced permeability and retention (EPR) effect. We previously reported a promising EPR enhancer-a nitric oxide (NO) donor-containing liposome (NO-LP)-which showed enhanced accumulation in tumor tissue. Herein, we study NO-LP in greater detail to clarify its practical use as an EPR enhancer. NO-LP was found to have advantages as a NO donor, including the ability to maintain NO donation over long periods of time, and a constant rate of NO-release irrespective of the environmental pH. NO-LP showed rapid accumulation in tumor tissue after injection (1 h), and then accumulation was continuously enhanced until 48 h. Enhanced NO-LP accumulation was observed specifically in tumor, while the accumulation in other organs remained relatively unchanged. The results obtained show the promising features of NO-LP as an EPR enhancer.