title: A survey on "Trojan Horse" peptides: opportunities, issues and controlled entry to "Troy".
abstract: 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".
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Jilin Medical College, Jilin 132013, PR China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address: shinianqiu2009@163.com.
authors.forename: Nian-Qiu
authors.initials: NQ
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address: qixr@bjmu.edu.cn.
authors.forename: Xian-Rong
authors.initials: XR
authors.lastname: Qi
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Bai
authors.initials: B
authors.lastname: Xiang
authors.affiliation: College of life science, Jilin University, Changchun 130012, PR China; State Key Laboratory of New Pharmaceutical Preparations and Excipients, China Shijiazhuang Pharmaceutical Group Co., Ltd., Shijiazhuang 050017, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002477:Cells / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D036103:Nanotechnology
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers
keywords: Cell-penetrating peptides; Clinical development; Controlled delivery strategies; Non-specificity; Organelle-specific delivery