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• W2907544549 endingPage "572" @default.
• W2907544549 startingPage "561" @default.
• W2907544549 abstract "The chimeric peptide HPRP-A1-iRGD, composed of a chemically conjugated tumor-homing/penetration domain (iRGD) and a cationic anticancer peptide domain (HPRP-A1), was used to study the effect of targeted modification to enhance the peptide’s specificity, penetration, and tumor accumulation ability. The iRGD domain exhibits tumor-targeting and tumor-penetrating activities by specifically binding to the neuropilin-1 receptor. Acting as a homing/penetration domain, iRGD contributed to enhancing the tumor selectivity, permeability, and targeting of HPRP-A1 by targeted receptor dependence. As the anticancer active domain, HPRP-A1 kills cancer cells by disrupting the cell membrane and inducing apoptosis. The in vitro membrane selectivity toward cancer cells, such as A549 and MDA-MB-23, and human umbilical vein endothelial cells (HUVECs), normal cells, the penetrability assessment in the A549 3D multiple cell sphere model, and the in vivo tumor-tissue accumulation test in the A549 xenograft model indicated that HPRP-A1-iRGD exhibited significant increases in the selectivity toward membranes that highly express NRP-1, the penetration distance in 3D multiple cell spheres, and the accumulation in tumor tissues after intravenous injection, compared with HPRP-A1 alone. The mechanism of the enhanced targeting ability of HPRP-A1-iRGD was demonstrated by the pull-down assay and biolayer interferometry test, which indicated that the chimeric peptide could specifically bind to the neuropilin-1 protein with high affinity. We believe that chemical conjugation with iRGD to increase the specificity, penetration, and tumor-tissue accumulation of HPRP-A1 is an effective and promising approach for the targeted modification of peptides as anticancer therapeutics." @default.
• W2907544549 created "2019-01-11" @default.
• W2907544549 creator A5036894207 @default.
• W2907544549 creator A5061140388 @default.
• W2907544549 creator A5062215362 @default.
• W2907544549 date "2018-12-28" @default.
• W2907544549 modified "2023-10-12" @default.
• W2907544549 title "Targeted Modification of the Cationic Anticancer Peptide HPRP-A1 with iRGD To Improve Specificity, Penetration, and Tumor-Tissue Accumulation" @default.
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• W2907544549 doi "https://doi.org/10.1021/acs.molpharmaceut.8b00854" @default.
• W2907544549 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30592418" @default.
• W2907544549 hasPublicationYear "2018" @default.
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