Artificial Cells and Organs Research Centre, Departments of Physiology, Medicine and Biomedical Engineering, McGill University, Montreal, Quebec, Canada H3G1Y6.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Jul-Aug;2(4):418-30. doi: 10.1002/wnan.95.
Unlike donor red blood cells (RBCs), blood substitutes can be treated to remove infective agents and can be used on the spot or in the ambulance in emergency without the time-consuming typing and cross-matching. Donor RBC requires storage at 4 degrees and is only good for 42 days, but blood substitutes can be stored for much longer time. For example, a bovine polyhemoglobin (PolyHb) can be stored at room temperature for more than 1 year. It has been shown as far back as 1957 that artificial RBC can be prepared with ultrathin polymer membranes of nanodimension thickness. To increase the circulation time, the first-generation engineered hemoglobin (Hb) is formed by using glutaraldehyde to crosslink Hb into soluble nanodimension PolyHb that has been tested clinically in patients. Further extension includes conjugated Hb, intramolecularly crosslinked Hb and recombinant Hb. For certain clinical uses, in addition to engineered Hb, we also need antioxidants to remove oxygen radicals to prevent injury from ischemia reperfusion. Thus, we use nanobiotechnology to prepare second-generation engineered Hb by assembling Hb together with superoxide dismutase (SOD) and catalase (CAT) to form a nanodimension soluble complex of polyhemoglobin (PolyHb)-CAT-SOD. A third generation system is to prepare nanodimension complete artificial RBCs that can circulate for sufficient length of time after infusion. One approach uses lipid vesicles to encapsulate hemoglobin (Hb). Another approach is to use biodegradable polymer-like polylactic acid or a copolymer of polyethylene glycol-polylactide (PEG-PLA) to form the membrane of nanodimension complete artificial RBC (www.artcell.mcgill.ca).
与供体红细胞（RBC）不同，血液替代品可以经过处理以去除感染性物质，并且可以在现场或救护车上使用，而无需耗时的血型鉴定和交叉配型。供体 RBC 需要在 4 摄氏度下储存，并且仅在 42 天内有效，但血液替代品可以储存更长的时间。例如，牛血红蛋白（PolyHb）可以在室温下储存超过 1 年。早在 1957 年就已经证明，可以使用具有纳米级厚度的超薄聚合物膜来制备人工 RBC。为了增加循环时间，第一代工程血红蛋白（Hb）是通过使用戊二醛将 Hb 交联成可溶的纳米级 PolyHb 制成的，这种 PolyHb 已经在患者中进行了临床测试。进一步的延伸包括共轭 Hb、分子内交联 Hb 和重组 Hb。对于某些临床用途，除了工程化 Hb，我们还需要抗氧化剂来清除氧自由基，以防止缺血再灌注损伤。因此，我们使用纳米生物技术通过将 Hb 与超氧化物歧化酶（SOD）和过氧化氢酶（CAT）组装在一起来制备第二代工程化 Hb，从而形成聚血红蛋白（PolyHb）-CAT-SOD 的纳米级可溶性复合物。第三代系统是制备纳米级完整的人工 RBC，在输注后可以循环足够长的时间。一种方法是使用脂质体来包裹血红蛋白（Hb）。另一种方法是使用可生物降解的聚合物样聚乳酸或聚乙二醇-聚乳酸共聚物（PEG-PLA）来形成纳米级完整人工 RBC 的膜（www.artcell.mcgill.ca）。
