Department of Medical Biotechnology, Faculty Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Protein Pept Lett. 2020;27(10):1029-1037. doi: 10.2174/0929866527666200413100120.
Bio-degradable nano-particles have many applications as drug delivery vehicles because of their good bio-availability, controlled release, low toxicity and potential for encapsulation. However, the most important obstacle to nanoparticulate drug delivery is elimination by macrophages which reduces the residence time of nanoparticles in the blood. To overcome this problem, the surface of the nanoparticle can be passivated by coating with Polyethylene glycol (PEG). However, the use of PEG has its own disadvantages. CD47 receptor acts as a self marker on the surface of many cells and inhibits phagocytosis. This study used a CD47 mimicry peptide as a substitute for PEG to fabricate "stealth" nanoliposome with reduced macrophage clearance.
Doxorubibin was used as a model drug because of its inherent fluorescence. Doxorubicin- containing liposomes were coated with different percentages of CD47 mimicry peptide (0.5% and 1%). PEG-functionalized doxorubicin-containing liposomes, were used as a comparator. The liposomal formulations were intravenously injected into mice. Serum was collected at pre-defined time points and tissue samples were taken at 24 hours. Fluorescence was used to determine the concentration doxorubicin in serum, heart, spleen, kidney, liver and lung tissues.
Tissue biodistribution and serum kinetic studies indicated that compared with PEG, the use of CD47 mimicry peptide increased the circulation time of doxorubicin in the circulation. Moreover, unwanted accumulation of doxorubicin in the reticuloendothelial tissues (liver and spleen), kidney and heart was significantly decreased by the CD47 mimicry peptide.
The use of a CD47 mimicry peptide on the surface of nanoliposomes improved the residence time of liposomal doxorubicin in the circulation. The accumulation of drug in non-target tissues was reduced, thereby potentially reducing toxicity.
生物可降解纳米粒子因其良好的生物利用度、控制释放、低毒性和封装潜力，在作为药物传递载体方面有许多应用。然而，纳米颗粒药物传递的最重要障碍是被巨噬细胞消除，这减少了纳米颗粒在血液中的停留时间。为了克服这个问题，可以通过用聚乙二醇（PEG）涂层来使纳米颗粒表面钝化。然而，PEG 的使用也有其自身的缺点。CD47 受体作为许多细胞表面的自我标志物，抑制吞噬作用。本研究使用 CD47 模拟肽作为 PEG 的替代品，来制备具有降低巨噬细胞清除率的“隐形”纳米脂质体。
阿霉素因其固有荧光而被用作模型药物。载有阿霉素的脂质体用不同百分比的 CD47 模拟肽（0.5%和 1%）进行涂层。将 PEG 功能化的载有阿霉素的脂质体作为对照。将脂质体制剂静脉注射到小鼠体内。在预先设定的时间点采集血清，并在 24 小时时采集组织样本。荧光用于确定血清、心脏、脾脏、肾脏、肝脏和肺组织中阿霉素的浓度。
组织分布和血清动力学研究表明，与 PEG 相比，使用 CD47 模拟肽增加了阿霉素在循环中的循环时间。此外，CD47 模拟肽显著减少了阿霉素在网状内皮组织（肝脏和脾脏）、肾脏和心脏中的不必要积累。
在纳米脂质体表面使用 CD47 模拟肽可延长脂质体阿霉素在循环中的停留时间。减少药物在非靶组织中的积累，从而潜在地降低毒性。
