Recent in vivo advances in cell-penetrating peptide-assisted drug delivery

ABSTRACT

Introduction: Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment.

Areas covered: In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP–cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA).

Expert Opinion: Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

Keywords:

• Activatable CPP
• cell penetrating peptides
• CPP
• drug delivery vectors
• in vivo delivery vectors
• peptide vectors

Article highlights

• Development of effective and safe methods to enhance the passage of biologically active macromolecules represents an important perspective for the future medicine. CPPs are important delivery vectors with unique properties that distinguish them from other types of vectors.

• It has been shown that various types of cargo have been effectively transported through biological barriers. These include small drug molecules, proteins, nucleic acid-based macromolecules, such as siRNA, antisense nucleotides and plasmid DNA.

• Two general types of vectorization have been used: covalent attachment to the CPP and nanoparticle formation with the cargo molecule. In addition, CPPs have been extensively used as a functional moiety in other types of carriers, such as liposomes.

• Various targeting strategies have been utilized to direct the delivery toward specific cells. Recent successful studies have used combined passive and active targeting designs.

Declaration of Interest

The authors were supported by EU through the European Regional Development Fund through the project Tumor-Tech (3.2.1001.11-0008) and the Centre of Excellence of Chemical Biology (3.2.0101.08-0017), by the Estonian Ministry of Education and Research through IUT20–26, by Swedish Research Council (VR-NT) and the Swedish Cancer Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.