Cell penetrating elastin-like polypeptides for therapeutic peptide delivery

被引:92
作者
Bidwell, Gene L., III [1 ]
Raucher, Drazen [1 ]
机构
[1] Univ Mississippi, Med Ctr, Dept Biochem, Jackson, MS 39216 USA
关键词
Elastin-like polypeptide; Thermal targeting; Therapeutic peptide; Cell penetrating peptide; c-Myc; p21; BLOOD-BRAIN-BARRIER; C-MYC; DOXORUBICIN CONJUGATE; INTRACELLULAR DELIVERY; ENHANCED PERMEABILITY; REGIONAL HYPERTHERMIA; MEDIATED ENDOCYTOSIS; PROTEIN TRANSDUCTION; CYCLE ARREST; SOLID TUMORS;
D O I
10.1016/j.addr.2010.05.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Current treatment of solid tumors is limited by side effects that result from the non-specific delivery of drugs to the tumor site. Alternative targeted therapeutic approaches for localized tumors would significantly reduce systemic toxicity. Peptide therapeutics are a promising new strategy for targeted cancer therapy because of the ease of peptide design and the specificity of peptides for their intracellular molecular targets. However, the utility of peptides is limited by their poor pharmacokinetic parameters and poor tissue and cellular membrane permeability in vivo. This review article summarizes the development of elastin-like polypeptide (ELP) as a potential carrier for thermally targeted delivery of therapeutic peptides (TP), and the use of cell penetrating peptides (CPP) to enhance the intracellular delivery of the ELF-fused TPs. CPP-fused ELPs have been used to deliver a peptide inhibitor of c-Myc function and a peptide mimetic of p21 in several cancer models in vitro, and both polypeptides are currently yielding promising results in in vivo models of breast and brain cancer. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:1486 / 1496
页数:11
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