Cell-penetrating peptides meditated encapsulation of protein therapeutics into intact red blood cells and its application.
Cell-penetrating peptides meditated encapsulation of protein therapeutics into intact red blood cells and its application.
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DOI：
10.1016/j.jconrel.2013.12.019
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发表时间：
2014-02-28
期刊：
影响因子：
--
通讯作者：
Yang VC
中科院分区：
文献类型：
--
作者：
He H;Ye J;Wang Y;Liu Q;Chung HS;Kwon YM;Shin MC;Lee K;Yang VC
基于红细胞（RBC）的药物载体似乎是最有吸引力的蛋白质药物，由于其无与伦比的生物相容性，生物降解性和循环寿命长。人们开发了许多将蛋白质药物包封到红细胞中的方法，然而，它们中的大多数诱导细胞膜的部分破坏，导致红细胞的物理和化学性质的不可逆改变。本文介绍了一种利用本实验室开发的细胞穿透肽--低分子量鱼精蛋白（LMWP）将蛋白质包埋到完整红细胞中的新方法。选择治疗急性淋巴细胞白血病（ALL）的主要药物之一L-天冬酰胺酶作为模型蛋白，以说明CPP介导的红细胞包封。此外，还综述了目前使用不同的L-天冬酰胺酶递送和包封方法治疗ALL的方法及其相关问题。
Red blood cells (RBCs) based drug carrier appears to be the most appealing for protein drugs due to their unmatched biocompatability, biodegradability, and long lifespan in the circulation. Numerous methods for encapsulating protein drugs into RBCs were developed, however, most of them induce partial disruption of the cell membrane, resulting in irreversible alterations in both physical and chemical properties of RBCs. Herein, we introduce a novel method for encapsulating proteins into intact RBCs, which was meditated by a cell penetrating peptide (CPP) developed in our lab—low molecular weight protamine (LMWP). L-asparaginase, one of the primary drugs used in treatment of acute lymphoblastic leukemia (ALL), was chosen as a model protein to illustrate the encapsulation into erythrocytes mediated by CPPs. In addition current treatment of ALL using different L-asparaginase delivery and encapsulation methods as well as their associated problems were also reviewed.
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