Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Durzyńska, Julia; Przysiecka, Łucja; Nawrot, Robert; Barylski, Jakub; Nowicki, Grzegorz; Warowicka, Alicja; Musidlak, Oskar; Goździcka-Józefiak, Anna

doi:10.1124/jpet.115.223305

Cited by 61 publications

(54 citation statements)

References 148 publications

(152 reference statements)

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“…For a long time, it was believed that CPPs would most likely enter cells by a passive process, which is temperature and receptor independent [46]. Endocytosis, being the most common process used by cells to absorb materials from their environment, can also be used as the translocation pathway of CPPs into cells [46,47].…”

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

“…that is mediated by positively charged residues interacting with phosphoinositides. A nonendocytotic, receptor-free, energyindependent cellular process is another mechanism of the CPP translocation across biologic membranes, including formation of inverted micelles, direct translocation through the lipid bilayer, and pore formation on the membrane [46,47,55,56]. CPPs with high content in cationic residues are first absorbed at the cell surface to the numerous anionic moieties, such as sialic or phospholipidic acid or heparan sulfate proteoglycans [46,57].…”

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

“…Endocytosis, being the most common process used by cells to absorb materials from their environment, can also be used as the translocation pathway of CPPs into cells [46,47]. Endocytosis is a generic term for several different processes, such as phagocytosis for large particles and pinocytosis for smaller ones, as well as receptor-mediated endocytosis in which clathrin or caveolin pits are involved [24,43,46]. Several receptors were uncovered to be involved in internalization of CPPs, such as chemokine receptors, syndecans [48,49], neuropilins [50,51], the family of integrins [52], homing sequences, and positively-charged scavenger receptors [53,54].…”

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

“…A nonendocytotic, receptor-free, energyindependent cellular process is another mechanism of the CPP translocation across biologic membranes, including formation of inverted micelles, direct translocation through the lipid bilayer, and pore formation on the membrane [46,47,55,56]. CPPs with high content in cationic residues are first absorbed at the cell surface to the numerous anionic moieties, such as sialic or phospholipidic acid or heparan sulfate proteoglycans [46,57]. Which of these mechanisms a CPP will use is dependent on such parameters as concentration, size (with cargo), temperature, cell type, and modifications of CPPs or their cargo [43,46,55].…”

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

See 4 more Smart Citations

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

Mohammadi

Zakeri–Milani

Golkar

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8)were prepared via non-covalent binding of the peptides and polyanions. Cytotoxicity and anti-proliferative activity were evaluated by MTT assay. Cellular uptake was examined by flow cytometry and fluorescence microscopy. The CPPs exhibited slight cytotoxicity.Binding of polyglutamate to CPPs (CPPs-E4 and CPPs-E8 nanoparticles) decreased their cytotoxicity. CPPs-E8 nanoparticles showed lower cytotoxicity than CPPs-E4 nanoparticles.Cellular uptake of K3W4K3-E8, K2W4K2-E8 and W3K4W3-E8 reached 100% with no difference between each of the mentioned CPPs and its nanoparticle at 50 µM. The antiproliferative activity of EPR was enhanced following conjugation to peptides and nanoparticles at 25 µM. CPPs-EPR-E4 and -E8 nanoparticles displayed higher antiproliferative activity than CPPs-EPR at 25 µM. CPPs-E8-EPR nanoparticles showed higher anti-proliferative activity than CPPs-E4-EPR. K3W4K3-E8-EPR nanoparticles exhibited the highest anti-proliferative activity at 25 µM. The synthesized peptide nanoparticles are proposed as suitable carriers for improving the intracellular delivery of EPR into tumor cells with low cytotoxicity and high antitumor activity.

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Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

See 3 more Smart Citations

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

Mohammadi

Zakeri–Milani

Golkar

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

show abstract

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Zhou

Zou

Cheng

et al. 2022

Clinical & Translational Med

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Due to the complex physiological structure, microenvironment and multiple physiological barriers, traditional anti‐cancer drugs are severely restricted from reaching the tumour site. Cell‐penetrating peptides (CPPs) are typically made up of 5–30 amino acids, and can be utilised as molecular transporters to facilitate the passage of therapeutic drugs across physiological barriers. Up to now, CPPs have widely been used in many anti‐cancer treatment strategies, serving as an excellent potential choice for oncology treatment. However, their drawbacks, such as the lack of cell specificity, short duration of action, poor stability in vivo, compatibility problems (i.e. immunogenicity), poor therapeutic efficacy and formation of unwanted metabolites, have limited their further application in cancer treatment. The cellular uptake mechanisms of CPPs involve mainly endocytosis and direct penetration, but still remain highly controversial in academia. The CPPs‐based drug delivery strategy could be improved by clever design or chemical modifications to develop the next‐generation CPPs with enhanced cell penetration capability, stability and selectivity. In addition, some recent advances in targeted cell penetration that involve CPPs provide some new ideas to optimise CPPs.

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Small Heat Shock Proteins B1 and B6: Which One is the Most Effective Adjuvant in Therapeutic HPV Vaccine?

et al. 2018

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Therapeutic human papillomaviruse (HPV) vaccines have the potential to inhibit the tumor growth by targeting HPV E6 and E7 oncoproteins. Among different vaccine strategies, DNA and protein-based approaches are the most effective candidates for stimulation of the immune responses against HPV infections. Our study was designed to assess the efficacy of small heat shock proteins B1 (Hsp27) and B6 (Hsp20) as an adjuvant accompanied by HPV16 E7 and hPP10-E7 antigens in tumor mouse model. A major key for successful DNA and protein transfer into cells is the development of delivery systems with high efficiency and low cytotoxicity. Herein, we used hPP10 and MPG cell penetrating peptides (CPPs) for protein and DNA delivery in vivo, respectively. Our data indicated that the combination of Hsp27 with the recombinant hPP10-E7 protein in homologous protein/protein (hPP10-E7 + Hsp27) and heterologous DNA/protein (pcDNA-E7 + MPG/ hPP10-E7 + Hsp27) significantly enhanced the E7-specific T cell responses. Indeed, these regimens induced high levels of IgG2a, IFN-γ and IL-2 directed toward Th1 responses and also Granzyme B secretion as compared to other immunization strategies, and also displayed complete protection more than 60 days after treatment. These data suggest that the use of Hsp27 as an adjuvant and MPG and hPP10 as a gene and protein carrier would represent promising applications for improvement of HPV therapeutic vaccines. © 2018 IUBMB Life, 70(10):1002-1011, 2018.

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Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Cited by 61 publications

References 148 publications

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Small Heat Shock Proteins B1 and B6: Which One is the Most Effective Adjuvant in Therapeutic HPV Vaccine?

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