Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, Kansas 66506, United States.
Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States.
ACS Appl Bio Mater. 2021 Sep 20;4(9):6974-6981. doi: 10.1021/acsabm.1c00643. Epub 2021 Aug 30.
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--glycero-3-phosphoglycerol, 1,2-distearoyl--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 () of BML is 3.71 mM s, which is comparable to the 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.
红细胞（RBC）构成了血管系统中绝大多数的细胞，它们一生中的大部分时间都在我们身体的每一个组织中弥漫的巨大血管网络中漫游。因此，任何一类必须留在循环系统中的治疗剂，如果由 RBC 携带，其输送都可能受益。为此，我们用 RBC 的膜对合成脂质体进行了再工程化，并将磁共振成像（MRI）造影剂钆与化疗药物阿霉素（DOX）一起整合到仿生脂质体（BML）中。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 1,2-二硬脂酰基-sn-甘油-3-磷酸甘油、1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺和钆结合脂质。这些合成磷脂与天然 RBC 膜融合，并通过挤出技术加载 DOX。对 BML 的物理化学性质、稳定性、（合成和天然 RBC 脂质之间的）融合性、磁性、药物负载、生物相容性和细胞毒性进行了表征。BML 的水动力直径为 180 ± 20nm，表面带负电荷 29 ± 2mV。BML 的纵向弛豫率（）为 3.71mM s，与商业造影剂 Magnevist 的 相当。此外，载 DOX 的 BML 表现出与游离 DOX 相似的细胞毒性模式。这些结果表明，拟议的 BML 系统具有用于 MRI 诊断应用和药物输送平台的潜力。
