ArticleJournal of peptide science : an official publication of the European Peptide Society2025
Cancer-Targeting Peptides Functionalized With Polyarginine Enables GRP78-Dependent Cell Uptake and siRNA Delivery Within the DU145 Prostate Cancer Cells.
Article in Journal of peptide science : an official publication of the European Peptide Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- GRP78 in viral pneumonia: dual regulatory mechanisms and translational prospects.Clinical and experimental medicine · 2026Review
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5 authors.
Funding
Abstract
This study investigated a peptide-based GRP78-targeting strategy for short-interfering (si) RNA delivery in cancer cells. Synthetic fluorescein-labeled amphiphilic peptides composed of the hydrophobic cell surface (cs) GRP78-targeting and hydrophilic, polycationic arginine-rich cell penetrating peptides demonstrated GRP78-dependent cell uptake in the DU145 prostate cancer cells, and to a lesser extent in the non-cancerous human lung fibroblast WI-38 cell line. Mechanistic studies revealed energy-dependent GRP78 receptor-mediated endocytosis of the GRP78-targeting peptide with polyarginine (W1-R9). The cytosolic accumulation of this peptide underscored its potential utility in siRNA delivery. Peptide:siRNA complexes formed stably condensed nanoparticles, with calcium functioning as an ionic stabilizer and additive promoting endosomal siRNA escape for RNA interference (RNAi) activity. Preliminary peptide-based siRNA transfections in the DU145 cells demonstrated that GRP78 knockdown led to an interplay in between pro-survival and cell death outcomes under ER stress induction. Thus, the GRP78-targeting polyarginine peptides enables efficient cell uptake for specific siRNA delivery in the DU145 cells. This class of bio-active synthetic peptides is important for the investigation of cancer biology, leading to the innovation of cancer-targeted gene delivery and therapy approaches.
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