作者：Shi NQ, Qi XR, Xiang B, Zhang Y
关键字：Cell-penetrating peptides,Clinical development,Non-specificity,Organelle-specific delivery, Controlled delivery strategies
论文来源：期刊
具体来源：J Controlled Release, 2014, 194: 53-70.(SCI,IF=7.441)
发表时间：2014年

Cell-penetrating

peptides (CPPs), often vividly termed as the “Trojan Horse” peptides, have attracted

considerable interest for the intracellular delivery of a wide range of cargoes,

such as small molecules, peptides, proteins, nucleic acids, contrast agents, nanocarriers

and so on. Some preclinical and clinical developments of CPP conjugates demonstrate

their promise as therapeutic agents for drug discovery. There is increasing

evidence to suggest that CPPs have the potential to cross several bio-barriers

(e.g., blood-brain barriers, intestinal mucosa, nasal mucosa and skin barriers).

Despite revolutionary process in many aspects, there are a lot of basic issues

unclear for these entities, such as internalization mechanisms, translocation efficiency,

translocation kinetics, metabolic degradation, toxicity, side effect,

distribution and non-specificity. Among them, non-specificity remains a major drawback

for the in vivo application of CPPs in the targeted delivery of cargoes. So

far, diverse organelle-specific CPPs or controlled delivery strategies have emerged

and improved their specificity. In this review, we will look at the opportunities

of CPPs in clinical development, bio-barriers penetration and nanocarriers delivery.

Then, a series of basic problems of CPPs will be discussed. Finally, this paper

will highlight the use of various controlled strategies in the organelle-specific

delivery and targeted delivery of CPPs. The purpose of this review will be to

emphasize most influential advance in this field and present a fundamental understanding

for challenges and utilizations of CPPs. This will accelerate their

translation as efficient vectors from the in vitro setting into the clinic

arena, and retrieve the entry art to “Troy”.

Keywords: Cell-penetrating peptides;

Clinical development; Non-specificity; Organelle-specific delivery; Controlled delivery

strategies.