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Improved Peptide-Targeted Liposome Design Through Optimized Peptide Hydrophilicity, Ethylene Glycol Linker Length, and Peptide Density

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Ligand-targeted liposomes are increasingly used as drug delivery carriers for cancer therapy, yet have not consistently produced successful outcomes. Here, we demonstrated the significant enhancement in cellular uptake of peptide-targeted liposomes by simultaneously increasing the hydrophilicity of the targeting peptide, optimizing the EG peptide-linker length, and using appropriate peptide surface density. We analyzed these parameters in a HER2-overexpressing breast cancer model system where the liposomes were functionalized with one of four distinct HER2-antagonist peptides to evaluate cellular uptake. Our results demonstrated that including a short oligolysine chain adjacent to the targeting peptide sequence effectively improved cellular uptake ∼6–10 fold when using an EG6-EG18 linker depending on the selected antagonist peptide. Uptake efficiency reached a maximum and a plateau with ∼2% peptide density with higher observed sensitivity at lower peptide densities for the more hydrophilic peptides. Taken together, these findings demonstrated the importance of optimizing liposome design for improved cellular uptake.
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Keywords: CELLULAR UPTAKE; HER2; LIGAND-TARGETED LIPOSOMES; PEPTIDE-LINKER; PEPTIDE-TARGETED

Document Type: Research Article

Publication date: August 1, 2015

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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