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pH-Promoted Release of a Novel Anti-Tumour Peptide by “Stealth” Liposomes: Effect of Nanocarriers on the Drug Activity in Cis-Platinum Resistant Cancer Cells

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Abstract

Purpose

To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug-resistant human cancer cell lines.

Methods

Peptide-loaded pH-sensitive PEGylated (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of the PpHL on the drug intracellular activity was investigated by the Western Blot analysis of proteins involved in the pathway affected by hTS inhibition.

Results

Although PpHL and nPpHL showed different sizes, surface hydrophilicities and serum stabilities, both carriers entrapped the drug efficiently and stably demonstrating a pH dependent release; moreover, the different behavior against J774 macrophage cells confirmed the ability of PEGylation in protecting liposomes from the reticuloendothelial system. Comparable effects were instead observed against C13* cells and biochemical data by immunoblot analysis indicated that PEGylated pH-sensitive liposomes do not modify the proteomic profile of the cells, fully preserving the activity of the biomolecule.

Conclusion

PpHL can be considered as efficient delivery systems for the new promising anti-cancer peptide.

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Abbreviations

[D-Gln4]LR:

New synthesized octapeptide (amminoacid sequence: LSCQLYQR) with inverted chirality at position 4 (corresponding to the amino acid glutamine) (LSCqLYQR)

DHFR:

Dihydrofolate reductase

EPR:

Enhanced permeation and retention

HSP 90-alpha:

Heat shock protein (HSP90AA1)

hTS:

Human thymidylate synthase

nPpHL:

Non-PEGylated peptide-loaded pH-sensitive liposomes

PBS:

Phosphate buffer solution

PEG:

Poly-ethylene-glycol

PpHL:

PEGylated peptide-loaded pH-sensitive liposomes

RES:

Reticuloendothelial system

TRAP1:

Tumour Necrosis Factor Receptor Associated Protein 1

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Author information

Author notes

  1. Maria Paola Costi and Eliana Leo contributed equally to this work.

Authors and Affiliations

  1. Department of Life Science, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy

    Francesca Sacchetti, Leda Severi, Eleonora Maretti, Valentina Iannuccelli, Glauco Ponterini, Maria Paola Costi & Eliana Leo

  2. Department Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Via Campi, 287, Modena, Italy

    Gaetano Marverti & Domenico D’Arca

  3. Department of Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 17-19, 44100, Ferrara, Italy

    Salvatore Pacifico

Authors
  1. Francesca Sacchetti
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  2. Gaetano Marverti
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  3. Domenico D’Arca
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  4. Leda Severi
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  5. Eleonora Maretti
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  6. Valentina Iannuccelli
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  7. Salvatore Pacifico
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  8. Glauco Ponterini
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  9. Maria Paola Costi
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  10. Eliana Leo
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Corresponding author

Correspondence to Eliana Leo.

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Sacchetti, F., Marverti, G., D’Arca, D. et al. pH-Promoted Release of a Novel Anti-Tumour Peptide by “Stealth” Liposomes: Effect of Nanocarriers on the Drug Activity in Cis-Platinum Resistant Cancer Cells. Pharm Res 35, 206 (2018). https://doi.org/10.1007/s11095-018-2489-z

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  • DOI: https://doi.org/10.1007/s11095-018-2489-z

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