University of Mississippi Medical Center, Department of Biochemistry, Jackson, 39216, USA.
Adv Drug Deliv Rev. 2010 Dec 30;62(15):1486-96. doi: 10.1016/j.addr.2010.05.003. Epub 2010 May 15.
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 ELP-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.
目前的实体肿瘤治疗受到副作用的限制，这些副作用是由于药物非特异性地输送到肿瘤部位所致。对于局限性肿瘤的替代靶向治疗方法将显著降低全身毒性。由于肽设计的容易性和肽对其细胞内分子靶标的特异性，肽治疗学是一种有前途的新的癌症靶向治疗策略。然而，肽的应用受到其差的药代动力学参数和差的组织和细胞膜通透性的限制。本文综述了弹性蛋白样多肽 (ELP) 作为热靶向递送达治疗性肽 (TP) 的潜在载体的发展，以及细胞穿透肽 (CPP) 用于增强 ELP 融合的 TP 的细胞内递送的用途。CPP 融合的 ELP 已被用于在几种体外癌症模型中递送 c-Myc 功能的肽抑制剂和 p21 的肽模拟物，这两种多肽目前在乳腺癌和脑癌的体内模型中都取得了有希望的结果。
