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Re-engineering a Liposome with Membranes of Red Blood Cells for Drug Delivery and Diagnostic Applications
ACS Applied Bio Materials ( IF 4.7 ) Pub Date : 2021-08-30 , DOI: 10.1021/acsabm.1c00643
Colin Ferrel 1, 2 , Sagar Rayamajhi 1, 2 , Tuyen Nguyen 3 , Ramesh Marasini 1, 2 , Tanvikhaa Saravanan 4 , Farah Deba 4 , Santosh Aryal 4
Affiliation  

Red blood cells (RBCs) make up the overwhelming majority of cells in the vascular system, spending most of their lives wandering the vast network of vessels that permeate every tissue of our bodies. Therefore, the delivery of any class of therapeutic agent that must stay in the circulatory system may benefit from being carried by RBCs. Toward this direction, we have re-engineered a synthetic liposome with the membranes of RBCs and incorporated a magnetic resonance imaging (MRI) contrast agent gadolinium along with the chemotherapeutic drug doxorubicin (DOX) to form a biomimetic liposome (BML). The BMLs proposed herein consist of biocompatible/biodegradable synthetic phospholipids, which include 1,2-distearoyl-sn-glycero-3-phosphoglycerol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and gadolinium-conjugated lipids. These synthetic phospholipids have been fused with a natural RBC membrane and are loaded with DOX using the extrusion technique. BMLs were characterized for their physicochemical properties, stability, fusogenic (between synthetic and natural lipid from RBC), magnetic, drug loading, biocompatibility, and cytotoxicity properties. BMLs had a hydrodynamic diameter of 180 ± 20 nm with a negative surface charge of 29 ± 2 mV. The longitudinal relaxivity (r1) of BML is 3.71 mM–1 s–1, which is comparable to the r1 of commercial contrast agent, Magnevist. In addition, DOX-loaded BML showed a cytotoxicity pattern similar to that of free DOX. These results showed the potential of using the proposed BML system for both MRI-based diagnostic applications and drug delivery platforms.

中文翻译:

重新设计具有红细胞膜的脂质体,用于药物输送和诊断应用

红细胞 (RBC) 构成血管系统中绝大多数的细胞,它们一生的大部分时间都在遍布我们身体每个组织的庞大血管网络中徘徊。因此,必须留在循环系统中的任何类别的治疗剂的递送可能受益于由红细胞携带。朝着这个方向,我们重新设计了一种具有红细胞膜的合成脂质体,并将磁共振成像 (MRI) 造影剂钆与化疗药物多柔比星 (DOX) 结合在一起,形成仿生脂质体 (BML)。本文提出的 BML 由生物相容性/可生物降解的合成磷脂组成,其中包括 1,2-二硬脂酰-sn-甘油-3-磷酸甘油、1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺和钆缀合的脂质。这些合成磷脂已与天然 RBC 膜融合,并使用挤压技术加载了 DOX。BML 的特征在于它们的物理化学特性、稳定性、融合性(介于来自 RBC 的合成脂质和天然脂质之间)、磁性、载药量、生物相容性和细胞毒性特性。BML 的流体动力学直径为 180 ± 20 nm,负表面电荷为 29 ± 2 mV。BML的纵向弛豫 ( r 1 ) 为 3.71 mM –1 s –1,与r 1相当商业造影剂,Magnevist。此外,载有 DOX 的 BML 显示出与游离 DOX 相似的细胞毒性模式。这些结果显示了将所提出的 BML 系统用于基于 MRI 的诊断应用程序和药物输送平台的潜力。
更新日期:2021-09-20
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