Self-assembly of amphiphilic helical-coiled peptide nanofibers and inhibition of fibril formation with curcumin

Daniel, Grace; Hilan, George; Ploeg, Lisa; Sabatino, David

doi:10.1016/j.bmcl.2024.129682

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2024

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Cited by 2 publications

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Exploring the interaction of curcumin with β-cyclodextrin and its binding with DNA: A combined spectroscopic and molecular docking study

Alghamdi,

Alterary,

Alarifi

et al. 2024

International Journal of Biological Macromolecules

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Exploring the interaction of curcumin with β-cyclodextrin and its binding with DNA: A combined spectroscopic and molecular docking study

Alghamdi,

Alterary,

Alarifi

et al. 2024

International Journal of Biological Macromolecules

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Spermidine and Chloroquine Enhance Peptide-Based pDNA Transfection Efficiency within the GRP78-Overexpressing DU145 Prostate Cancer Cells

Daniel,

Collak,

Hilan

et al. 2024

Preprint

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This study describes a peptide-based formulation for plasmid gene (pDNA) delivery within the GRP78-overexpressing prostate cancer (DU145) cells. The GRP78-targeting sequence (WIFPWIQL) extended with the nona-arginine (R9) cell-penetrating peptide (WIFPWIQL-R9) effectively enabled capture and release of pDNA, while conferring serum stability, according to agarose gel electrophoresis. Characterization studies based on transmission electron microscopy revealed the formation of stably condensed peptide:pDNA nanoparticles (<200 nm) at excess peptide nitrogen (N) to pDNA phosphate (P) stoichiometric ratios (10:1 N/P) and with CaCl2 functioning as an ionic stabilizer, that rendered the nanoparticles applicable to cell biology. Confocal imaging of the FITC-labeled peptide:pDNA formulation indicated cell uptake and intracellular entrapment within endosomes that restricted pDNA gene expression in the DU145 cells. Optimization studies with a reporter plasmid Green Fluorescent Protein (pGFP) revealed spermidine and chloroquine as the most effective additives for enhancing peptide-based transfection efficiency. Furthermore, blocking with anti-GRP78 confirmed the GRP78-dependent mechanism for cell uptake. Thus, peptide-targeting of GRP78 allows for selective binding and entry within the GRP78-overexpressing cancer cells for gene (pDNA) delivery. Transfection of the tumor suppressor p53-expression vector using the optimized peptide-based transfection conditions revealed elevated levels of p53 within the DU145 prostate cancer cells. These findings indicate the potential anti-cancer utility of the GRP78-targeting peptide gene (pDNA) delivery system.

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Self-assembly of amphiphilic helical-coiled peptide nanofibers and inhibition of fibril formation with curcumin

Cited by 2 publications

References 50 publications

Exploring the interaction of curcumin with β-cyclodextrin and its binding with DNA: A combined spectroscopic and molecular docking study

Exploring the interaction of curcumin with β-cyclodextrin and its binding with DNA: A combined spectroscopic and molecular docking study

Spermidine and Chloroquine Enhance Peptide-Based pDNA Transfection Efficiency within the GRP78-Overexpressing DU145 Prostate Cancer Cells

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