title: CPP-Assisted Intracellular Drug Delivery, What Is Next?
abstract: For the past 20 years, we have witnessed an unprecedented and, indeed, rather miraculous event of how cell-penetrating peptides (CPPs), the naturally originated penetrating enhancers, help overcome the membrane barrier that has hindered the access of bio-macromolecular compounds such as genes and proteins into cells, thereby denying their clinical potential to become potent anti-cancer drugs. By taking the advantage of the unique cell-translocation property of these short peptides, various payloads of proteins, nucleic acids, or even nanoparticle-based carriers were delivered into all cell types with unparalleled efficiency. However, non-specific CPP-mediated cell penetration into normal tissues can lead to widespread organ distribution of the payloads, thereby reducing the therapeutic efficacy of the drug and at the same time increasing the drug-induced toxic effects. In view of these challenges, we present herein a review of the new designs of CPP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy in combating tumor oncology.
authors.affiliation: Collaborative Innovation Center of Chemical Science and Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. jasmineye2014@163.com.|Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. jasmineye2014@163.com.
authors.forename: Junxiao
authors.initials: J
authors.lastname: Ye
authors.affiliation: Collaborative Innovation Center of Chemical Science and Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. liuergang@hotmail.com.|Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. liuergang@hotmail.com.
authors.forename: Ergang
authors.initials: E
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. yuzhilinancy@163.com.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. 13512232903@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Pei
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. annanchensunhui@foxmail.com.
authors.forename: Sunhui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Collaborative Innovation Center of Chemical Science and Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. 15122802060@126.com.|Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. 15122802060@126.com.
authors.forename: Pengwei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinjudaero, Jinju, Gyeongnam 660-751, Korea. shinmc@gnu.ac.kr.
authors.forename: Meong-Cheol
authors.initials: MC
authors.lastname: Shin
authors.affiliation: Collaborative Innovation Center of Chemical Science and Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. junbo_gong@tju.edu.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Gong
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. hehuining@tmu.edu.cn.
authors.forename: Huining
authors.initials: H
authors.lastname: He
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling, Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. vcyang@med.umich.edu.|Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA. vcyang@med.umich.edu.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004705:Endocytosis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000188:drug therapy*; D010539:Permeability; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers
keywords: CPPs; intracellular delivery; pH and enzyme triggered drug delivery system