作者：Shi NQ, Qi XR, Xiang B, Zhang Y
關鍵字：Cell-penetrating peptides,Clinical development,Non-specificity,Organelle-specific delivery, Controlled delivery strategies
論文來源：期刊
具體來源：J Controlled Release, 2014, 194: 53-70.(SCI,IF=7.441)
發表時間：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.
