title: Cell-penetrating properties of the transactivator of transcription and polyarginine (R9) peptides, their conjugative effect on nanoparticles and the prospect of conjugation with arsenic trioxide.
abstract: Cell-penetrating peptides (CPPs) are short chains of amino acids with the distinct ability to cross cell plasma membranes. They are usually between seven and 30 residues in length. The mechanism of action is still a highly debated subject among researchers; it seems that a commonality between all CPPs is the presence of positively charged residues within the amino acid chain. Polyarginine and the transactivator of transcription peptide are two widely used CPPs. One distinct application of these CPPs is the ability to further enhance the therapeutic properties of a range of different agents. One group of agents of particular importance are nanoparticles (NPs). Most NPs have no mechanism for cellular uptake. Hence, by conjugating CPPs to NPs, the amount of NPs taken up by cells can be increased, and therefore, the therapeutic benefits can be maximized. Some examples of this will be explored further in this review. In addition to CPPs, the concept of conjugation with the anticancer drug arsenic trioxide is reviewed and the prospect of transactivator of transcription-conjugated arsenic trioxide albumin microspheres is also discussed. Recent locked nucleic acid technology to stabilize nucleotides (RNA or DNA) aptamer complexes able to target cancer cells more specifically and selectively to kill tumour cells and spare normal body cells. NPs tagged with modified locked nucleic acid-aptamers have the potential to kill cancer cells more specifically and effectively while sparing normal cells.
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research, Centre for Biotechnology and Interdisciplinary Biosciences, Institute for Technology and Research Innovation, Geelong Technology Precinct, Deakin University, Vic., Australia. jagat.kanwar@deakin.edu.au
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
authors.forename: Jessica
authors.initials: J
authors.lastname: Gibbons
authors.forename: Anita K
authors.initials: AK
authors.lastname: Verma
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Kanwar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010087:Oxides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D015534:Trans-Activators / Q000737:chemistry*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D010087:Oxides; D010446:Peptide Fragments; D010455:Peptides; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus; C422951:tat peptide (48-60), Human immunodeficiency virus 1; C015462:polyarginine; D000077237:Arsenic Trioxide