Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

简介：可生物降解的纳米颗粒具有良好的生物利用度，受控释放，低毒性和封装潜力，因此具有许多作为药物传递载体的应用。然而，纳米颗粒药物递送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）涂覆来钝化纳米颗粒的表面。然而，使用PEG有其自身的缺点。CD47受体充当许多细胞表面的自标记，并抑制吞噬作用。这项研究使用CD47模拟肽作为PEG的替代品，以制备具有减少巨噬细胞清除率的“隐形”纳米脂质体。

方法：阿霉素因其固有的荧光性而被用作模型药物。用不同百分比的CD47模拟肽（0.5％和1％）包被含阿霉素的脂质体。PEG-官能化的含阿霉素的脂质体用作比较剂。将脂质体制剂静脉内注射到小鼠中。在预定的时间点收集血清，并在24小时时采集组织样品。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。

结果：组织生物分布和血清动力学研究表明，与PEG相比，CD47模拟肽的使用增加了阿霉素在循环系统中的循环时间。此外，CD47模拟肽显着减少了阿霉素在网状内皮组织（肝和脾），肾脏和心脏中的多余积聚。

结论：在纳米脂质体表面使用CD47模仿肽可改善阿霉素脂质体在循环中的停留时间。减少了药物在非目标组织中的积累，从而潜在地降低了毒性。