Cancer-Targeting Peptides Functionalized With Polyarginine Enables GRP78-Dependent Cell Uptake and siRNA Delivery Within the DU145 Prostate Cancer Cells.

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

SUBMITTER: Hilan G 

PROVIDER: S-EPMC11836551 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature