L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL).

L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL).
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DOI:
10.1016/j.jconrel.2009.06.027
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发表时间:
2009-11-03
影响因子:
10.8
通讯作者:
Yang, Victor C.
Yang, Victor C.
中科院分区:
医学1区
文献类型:
--
作者:
Kwon, Young Min;Chung, Hee Sun;Moon, Cheol;Yockman, James;Park, Yoon Jeong;Gitlin, Scott D.;David, Allan E.;Yang, Victor C.

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As a primary drug for the treatment of acute lymphoblastic leukemia (ALL), encapsulation of L-asparaginase (ASNase) into red blood cells (RBC) has been popular to circumvent immunogenicity from the exogenous protein. Unlike existing methods that perturbs RBC membranes, we introduce a novel method of RBC-incorporation of proteins using the membrane-traslocating low molecular weight protamine (LMWP). Confocal study of fluorescence-labeled LMWP-ovalbumin, as a model protein conjugate, has shown significant fluorescence inside RBCs. Surface morphology by scanning electron microscopy of the RBCs loaded with LMWP-ASNase was indistinguishable with normal RBCs. These drug loaded RBCs also closely resembled the profile of the native erythrocytes in terms of osmotic fragility, oxygen dissociation and hematological parameters. The in vivo half-life of enzyme activity after administering 8 units of RBC/LMWP-ASNase in DBA/2 mice was prolonged to 4.5±0.5 days whereas that of RBCs loaded with ASNase via a hypotonic method was 2.4±0.7 days. Furthermore, the mean survival time of DBA/2 mice bearing mouse lymphoma cell L5178Y was improved by ∼44% compared to the saline control group after treatment with the RBC loaded enzymes. From these data, an innovative, novel method for encapsulating proteins into intact and fully functional erythrocytes was established for potential treatment of ALL.
DOI: 10.1172/jci106985
发表时间: 1972-01-01
影响因子: 15.9
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