Harnessing the power of cell-penetrating peptides: activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents.
Harnessing the power of cell-penetrating peptides: activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents.
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利用细胞穿透肽的力量：可激活载体，用于靶向全身递送癌症治疗剂和显像剂。
DOI：
10.1002/wnan.1197
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发表时间：
2013-01
影响因子：
8.6
通讯作者：
Chilkoti, Ashutosh
中科院分区：
文献类型：
--
作者：
MacEwan, Sarah R.;Chilkoti, Ashutosh
癌症治疗药物和显像剂的靶向输送旨在增强这些分子在实体肿瘤中的积累，同时避免在健康组织中摄取。通过增强渗透性和滞留效应以及主动靶向策略，被动靶向一直在追求肿瘤特异性的积累。主动靶向是通过载体的功能化来实现的，以允许载体和肿瘤环境之间的特定相互作用。载体的功能化具有与癌细胞上过度表达的受体特异性相互作用的配体，是主动肿瘤靶向的经典方法。细胞穿透肽(CPPs)提供了一种非特异性和非受体依赖的机制来增强细胞摄取，这为传统的主动靶向方法提供了一种令人兴奋的替代方法。虽然CPP介导的内化的非特异性具有耐人寻味的潜力，使这种方法适用于广泛的肿瘤类型，但它们的混杂是其系统应用的临床实用的重大障碍。已经研究了许多方法来选择性地开启系统递送的CPP功能化载体的功能，特别是在肿瘤中，以实现癌症治疗药物和显像剂的靶向递送。
Targeted delivery of cancer therapeutics and imaging agents aims to enhance the accumulation of these molecules in a solid tumor while avoiding uptake in healthy tissues. Tumor-specific accumulation has been pursued with passive targeting by the enhanced permeability and retention effect, as well as with active targeting strategies. Active targeting is achieved by functionalization of carriers to allow specific interactions between the carrier and the tumor environment. Functionalization of carriers with ligands that specifically interact with overexpressed receptors on cancer cells represents a classic approach to active tumor targeting. Cell-penetrating peptides (CPPs) provide a non-specific and receptor-independent mechanism to enhance cellular uptake that offers an exciting alternative to traditional active targeting approaches. While the non-specificity of CPP-mediated internalization has the intriguing potential to make this approach applicable to a wide range of tumor types, their promiscuity is, however, a significant barrier to their clinical utility for systemically administered applications. Many approaches have been investigated to selectively turn on the function of systemically delivered CPP-functionalized carriers specifically in tumors to achieve targeted delivery of cancer therapeutics and imaging agents.
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