Tatp-mediated intracellular delivery of pharmaceutical nanocarriers

2007 ◽  
Vol 35 (4) ◽  
pp. 816-820 ◽  
Author(s):  
V.P. Torchilin
Keyword(s):  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Cell Penetrating ◽  
Biological Target ◽  
Transactivator Of Transcription ◽  
Pharmaceutical Nanocarriers ◽  
Stimuli Sensitive

CPPs (cell-penetrating peptides), including Tatp (transactivator of transcription peptide), have been successfully used for intracellular delivery of a wide variety of cargoes including various nanoparticulate pharmaceutical carriers such as liposomes, micelles and nanoparticles. Here, we will consider the major results obtained in this area with emphasis on Tatp-mediated delivery of liposomes and various transfection vectors. We will also address the development of ‘smart’ stimuli-sensitive nanocarriers, where the cell-penetrating function can only be activated when the nanocarrier is inside the biological target, thus minimizing the interaction with non-target cells.

Therapeutic delivery using cell-penetrating peptides

2013 ◽  
Vol 5 (3) ◽  
Author(s):  
Rupa R. Sawant ◽  
Niravkumar R. Patel ◽  
Vladimir P. Torchilin
Keyword(s):  
Small Molecules ◽  
Therapeutic Agent ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Current Status ◽  
Unique Challenge ◽  
Large Molecules ◽  
Therapeutic Delivery ◽  
Cell Penetrating ◽  
Stimuli Sensitive

AbstractIntracellular delivery of promising therapeutic agents as well as nanocarriers presents a unique challenge. However, with the discovery of the cell-penetrating peptides (CPPs), overcoming this obstacle seems more plausible. In many cases, CPPs conjugated with therapeutic agent or therapeutic agent loaded-nanoparticles have shown promising results via increased cellular uptake. In this review, the current status of CPPs for the intracellular delivery of not just potential therapeutic small molecules but also large molecules like peptides, nucleic acids and nanocarriers is discussed. In addition, the design of ‘smart stimuli-sensitive nanocarrier’ to overcome the non-target-specificity of CPPs is also described.

scholarly journals Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules

2005 ◽  
Vol 390 (2) ◽  
pp. 407-418 ◽  
Author(s):  
Catherine de Coupade ◽  
Antonio Fittipaldi ◽  
Vanessa Chagnas ◽  
Matthieu Michel ◽  
Sophie Carlier ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Mammalian Cells ◽  
Heparan Sulphate ◽  
Intracellular Delivery ◽  
Membrane Lipid ◽  
Cell Penetrating Peptides ◽  
Heparin Binding ◽  
Independent Manner ◽  
Cell Penetrating

Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell® peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell® peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell® peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.

scholarly journals Stimuli-Sensitive Cell Penetrating Peptide-Modified Nanocarriers

Processes ◽  
2019 ◽  
Vol 7 (10) ◽  
pp. 727 ◽  
Author(s):  
Perche
Keyword(s):  
Therapeutic Index ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Cellular Internalization ◽  
Normal Tissues ◽  
Formidable Challenge ◽  
Cell Penetrating ◽  
Stimuli Sensitive ◽  
Responsive Cell

The integration of drugs into nanocarriers favorably altered their pharmacodynamics and pharmacokinetics compared to free drugs, and increased their therapeutic index. However, selective cellular internalization in diseased tissues rather than normal tissues still presents a formidable challenge. In this chapter I will cover solutions involving environment-responsive cell-penetrating peptides (CPPs). I will discuss properties of CPPs as universal cellular uptake enhancers, and the modifications imparted to CPP-modified nanocarriers to confine CPP activation to diseased tissues.

scholarly journals Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

2019 ◽  
Vol 10 (4) ◽  
pp. 45 ◽  
Author(s):  
Anderson ◽  
Hobbs ◽  
Gwenin ◽  
Ball ◽  
Bennie ◽  
...  
Keyword(s):  
Magnetic Nanoparticle ◽  
Genetically Modified ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Tumour Site ◽  
Enzyme Prodrug Therapy ◽  
Delivery Vector ◽  
Cell Penetrating ◽  
Subsequent Activation ◽  
Potential Use

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells.

Cell-penetrating-peptide-based delivery of oligonucleotides: an overview

2007 ◽  
Vol 35 (4) ◽  
pp. 775-779 ◽  
Author(s):  
R. Abes ◽  
A.A. Arzumanov ◽  
H.M. Moulton ◽  
S. Abes ◽  
G.D. Ivanova ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Peptide Delivery ◽  
Cell Penetrating Peptide ◽  
Cellular Internalization ◽  
Structure Activity ◽  
Cell Penetrating ◽  
Transactivator Of Transcription ◽  
Endocytic Vesicles ◽  
Oligonucleotide Analogues ◽  
Phosphorodiamidate Morpholino Oligomers

Cationic CPPs (cell-penetrating peptides) have been used largely for intracellular delivery of low-molecular-mass drugs, biomolecules and particles. Most cationic CPPs bind to cell-associated glycosaminoglycans and are internalized by endocytosis, although the detailed mechanisms involved remain controversial. Sequestration and degradation in endocytic vesicles severely limits the efficiency of cytoplasmic and/or nuclear delivery of CPP-conjugated material. Re-routing the splicing machinery by using steric-block ON (oligonucleotide) analogues, such as PNAs (peptide nucleic acids) or PMOs (phosphorodiamidate morpholino oligomers), has consequently been inefficient when ONs are conjugated with standard CPPs such as Tat (transactivator of transcription), R9 (nona-arginine), K8 (octalysine) or penetratin in the absence of endosomolytic agents. New arginine-rich CPPs such as (R-Ahx-R)4 (6-aminohexanoic acid-spaced oligo-arginine) or R6 (hexa-arginine)–penetratin conjugated to PMO or PNA resulted in efficient splicing correction at non-cytotoxic doses in the absence of chloroquine. SAR (structure–activity relationship) analyses are underway to optimize these peptide delivery vectors and to understand their mechanisms of cellular internalization.

Intracellular Delivery of Histidine and Arginine Rich Cell Penetrating Peptides into HeLa cell Line

2015 ◽  
Vol 5 (4) ◽  
pp. 695
Author(s):  
Shikha Saxena ◽  
Deepika Bisht ◽  
Basavaraj Sajjanar ◽  
Arvind Kumar Singh ◽  
Aditya Prasad Sahoo ◽  
...  
Keyword(s):  
Hela Cell ◽  
Cell Line ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Hela Cell Line ◽  
Cell Penetrating
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