scholarly journals Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems

2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Eisaku Kondo ◽  
Ken Saito ◽  
Yuichi Tashiro ◽  
Kaeko Kamide ◽  
Shusei Uno ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Molecular Delivery ◽  
Cell Penetrating

scholarly journals Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems

2020 ◽  
Vol 21 (20) ◽  
pp. 7502
Author(s):  
Ona Illa ◽  
José-Antonio Olivares ◽  
Nerea Gaztelumendi ◽  
Laura Martínez-Castro ◽  
Jimena Ospina ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Conformational Structure ◽  
Intracellular Accumulation ◽  
Standard Drug ◽  
Cell Line Hela ◽  
Computational Calculations ◽  
Cell Penetrating

Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 μM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 μM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.

scholarly journals P01.04 Lentiviral protein Vpx delivery systems as potential weapons to improve cytarabine treatment response against acute myeloid leukemia

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A4.2-A5
Author(s):  
R Nair ◽  
H Baldauf
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Response ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Proteasomal Degradation ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Full Length ◽  
Cell Penetrating ◽  
Acute Myeloid

BackgroundAcute myeloid leukemia (AML) is an aggressive cancer of the blood, where malignant myeloid blasts accumulate in the bone marrow. One of the challenges of effective AML treatment is resistance to cytarabine (or ara-C), a standard AML chemotherapeutic drug used in front-line treatment today. In 2017, Schneider et al. reported the dNTPase sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) to be a targetable biomarker for ara-C treatment response.1 The intracellular triphosphorylated active form of ara-C, ara-CTP, was recognized as a substrate by SAMHD1 and is hydrolyzed back to ara-C. This led to a decrease in the amount of ara-CTP within the cells and consequently reduced cytotoxicity.1 SAMHD1 can be targeted by the lentiviral accessory protein Vpx for proteasomal degradation by interacting with the proteasomal degradation complex and SAMHD1. This study aims to use Vpx to target SAMHD1 in AML cells to improve ara-C sensitivity.Materials and MethodsIn order to manipulate SAMDH1 levels using Vpx, different Vpx delivery systems were developed. These are virus-like particles (VLPs) packaged with different homologs of Vpx from Simian Immunodeficiency Viruses (SIV) and HIV-2, and cell-penetrating peptides (CPPs) bound to either a 67 amino acid truncated SIVmac Vpx (67aaVpx) or to the WT full-length form. Two different CPPs were used in the synthesis: TAT and CPP44. The latter was chosen, as significantly better uptake of the CPP was observed in AML cell lines and primary blasts compared to healthy PBMCs.2.ResultsUpon treating AML cell lines with the VLPs, we observed different SAMHD1-degradation capacities of the different Vpx homologs. SIVmac239 Vpx and HIV-2 7312a Vpx were most efficiently loaded into the VLPs, showed the highest SAMHD1-degradation and improved ara-C sensitivity up to 80-fold. In contrast, HIV-2 Rod9 Vpx did not show any SAMHD1 degradation or improvement in ara-C sensitivity despite its high packaging efficiency in the VLPs. As for the CPPs, CPP44 bound to 67aaVpx showed better uptake and SAMHD1 degradation compared to the TAT bound 67aaVpx in THP-1 cells, which is an AML cell line with high SAMHD1 expression levels. Upon co-treatment with ara-C, up to a 5-fold reduction in IC50 was observed when treated with CPP44-bound 67aaVpx. In order to increase the efficiency further, full-length Vpx-bound CPPs will be prepared, and trials using these CPPs are currently underway. ConclusionsWe demonstrate that inducing SAMHD1 degradation by Vpx delivered via VLPs or CPPs efficiently improved ara-C sensitivity in AML cell lines. Combining a Vpx delivery system with treatments containing ara-C might improve treatment outcomes in SAMHD1-high patients who are otherwise non-responsive.ReferencesSchneider C, Oellerich T, Baldauf HM, Schwarz SM, Thomas D, Flick R, et al. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia. Nat Med 2017 Feb 1;23(2):250–5.Kondo E, Saito K, Tashiro Y, Kamide K, Uno S, Furuya T, et al. Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems. Nat Commun 2012 Jan 17;3(1):951.Disclosure InformationR. Nair: None. H. Baldauf: None.

scholarly journals Cell-penetrating Peptides: Efficient Vectors for Vaccine Delivery

2019 ◽  
Vol 16 (5) ◽  
pp. 430-443 ◽  
Author(s):  
Jieru Yang ◽  
Yacheng Luo ◽  
Mohini Anjna Shibu ◽  
Istvan Toth ◽  
Mariusz Skwarczynskia
Keyword(s):  
Drug Transport ◽  
Vaccine Delivery ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Antigen Delivery ◽  
Antigen Uptake ◽  
Cell Penetrating ◽  
The Stability ◽  
Antigen Presenting

Subunit vaccines are composed of pathogen fragments that, on their own, are generally poorly immunogenic. Therefore, the incorporation of an immunostimulating agent, e.g. adjuvant, into vaccine formulation is required. However, there are only a limited number of licenced adjuvants and their immunostimulating ability is often limited, while their toxicity can be substantial. To overcome these problems, a variety of vaccine delivery systems have been proposed. Most of them are designed to improve the stability of antigen in vivo and its delivery into immune cells. Cell-penetrating peptides (CPPs) are especially attractive component of antigen delivery systems as they have been widely used to enhance drug transport into the cells. Fusing or co-delivery of antigen with CPPs can enhance antigen uptake, processing and presentation by antigen presenting cells (APCs), which are the fundamental steps in initiating an immune response. This review describes the different mechanisms of CPP intercellular uptake and various CPP-based vaccine delivery strategies.

scholarly journals Novel approaches in development of cell penetrating peptides

2021 ◽  
Vol 9 (1) ◽  
pp. 1-7
Author(s):  
Vatsal R. Shah ◽  
Yamini D. Shah ◽  
Mansi N. Athalye
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Delivery Systems ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Effective Drug ◽  
Cell Penetrating ◽  
Potential Benefits ◽  
Novel Approaches

Therapeutic cargos which are impermeable to the cell can be delivered by cell penetrating peptides (CPPs). CPP-cargo complexes accumulate by endocytosis inside the cells but they fail to reach the cytosolic space properly as they are often trapped in the endocytic organelles. Here the CPP mediated endosomal escape and some strategies used to increase endosomal escape of CPP-cargo conjugates are discussed with evidence. Potential benefits can be obtained by peptides such as reduction in side effects, biocompatibility, easier synthesis and can be obtained at lower administered doses. The particular peptide known as cell penetrating peptides are able to translocate themselves across membrane with the carrier drugs with different mechanisms. This is of prime importance in drug delivery systems as they have capability to cross physiological membranes. This review describes various mechanisms for effective drug delivery and associated challenges

scholarly journals Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes

2021 ◽  
Author(s):  
Joan Gimenez-Dejoz ◽  
Keiji Numata
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Biological Membranes ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Cell Penetrating ◽  
Target Molecules

Peptide-based delivery systems that deliver target molecules into cells have been gaining traction. These systems need cell-penetrating peptides (CPPs), which have the remarkable ability to penetrate into biological membranes and...

The rational design of cell-penetrating peptides for application in delivery systems

Peptides ◽  
2019 ◽  
Vol 121 ◽  
pp. 170149 ◽  
Author(s):  
Ziyao Kang ◽  
Guihua Ding ◽  
Zhao Meng ◽  
Qingbin Meng
Keyword(s):  
Rational Design ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Cell Penetrating

Cell-penetrating Peptides as Nucleic Acid Delivery Systems: From Biophysics to Biological Applications

2013 ◽  
Vol 19 (16) ◽  
pp. 2895-2923 ◽  
Author(s):  
Sara Trabulo ◽  
Ana L. Cardoso ◽  
Ana M. S. Cardoso ◽  
Catarina M. Morais ◽  
Amalia S. Jurado ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Nucleic Acid Delivery ◽  
Biological Applications ◽  
Cell Penetrating

scholarly journals Cell-Penetrating Peptides—Mechanisms of Cellular Uptake and Generation of Delivery Systems

2010 ◽  
Vol 3 (4) ◽  
pp. 961-993 ◽  
Author(s):  
Sara Trabulo ◽  
Ana Luísa Cardoso ◽  
Miguel Mano ◽  
Maria C. Pedroso De Lima
Keyword(s):  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Cell Penetrating

scholarly journals Applicability and Limitations of Cell-Penetrating Peptides in Noncovalent Mucosal Drug or Carrier Delivery Systems

2016 ◽  
Vol 105 (2) ◽  
pp. 747-753 ◽  
Author(s):  
Noriyasu Kamei ◽  
Ebbe Juel Bech Nielsen ◽  
Takayuki Nakakubo ◽  
Yukina Aoyama ◽  
Ulrik Lytt Rahbek ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Cell Penetrating
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