Enzyme Technology Laboratory, Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, RJ, Brazil.
Laboratory of Toxinology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil.
Int J Mol Sci. 2021 Oct 15;22(20):11120. doi: 10.3390/ijms222011120.
The bacterial enzyme asparaginase is the main treatment option for acute lymphoblastic leukemia. However, it causes side effects, such as immunological reactions, and presents undesirable glutaminase activity. As an alternative, we have been studying asparaginase II from , coded by gene, which was cloned and expressed in The recombinant asparaginase (ASP) presented antileukemic activity and a glutaminase activity 100 times lower in comparison to its asparaginase activity. In this work, we describe the development of a delivery system for ASP via its covalent attachment to functionalized polyethylene glycol (PEG) polymer chains in the outer surface of liposomes (ASP-enzymosomes). This new delivery system demonstrated antiproliferative activity against K562 (chronic myeloid leukemia) and Jurkat (acute lymphocytic leukemia) cell lines similar to that of ASP. The antiproliferative response of the ASP-enzymosomes against the Jurkat cells suggests equivalence to that of the free commercial asparaginase (Aginasa). Moreover, the ASP-enzymosomes were stable at 4 °C with no significant loss of activity within 4 days and retained 82% activity up to 37 days. Therefore, ASP-enzymosomes are a promising antileukemic drug.
细菌酶 asparaginase 是治疗急性淋巴细胞白血病的主要选择。然而，它会引起副作用，如免疫反应，并表现出不理想的谷氨酰胺酶活性。作为替代方法，我们一直在研究来自 的 asparaginase II，由 基因编码，该基因已在 中克隆和表达。重组 asparaginase（ASP）具有抗白血病活性，其谷氨酰胺酶活性比其 asparaginase 活性低 100 倍。在这项工作中，我们描述了通过将 ASP 共价连接到脂质体（ASP-酶体）外表面的功能化聚乙二醇（PEG）聚合物链上来开发 ASP 的递送系统。与 ASP 相比，这种新的递送系统对 K562（慢性髓性白血病）和 Jurkat（急性淋巴细胞白血病）细胞系表现出类似的增殖活性。ASP-酶体对 Jurkat 细胞的增殖抑制反应表明与游离的商业 asparaginase（Aginasa）相当。此外，ASP-酶体在 4°C 下稳定，在 4 天内没有明显的活性损失，并且在 37 天内保持 82%的活性。因此，ASP-酶体是一种有前途的抗白血病药物。
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