fulltext.study @t Gmail

Dual-modified liposomes with a two-photon-sensitive cell penetrating peptide and NGR ligand for siRNA targeting delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
5723 419 2015 13 PDF Available
Title
Dual-modified liposomes with a two-photon-sensitive cell penetrating peptide and NGR ligand for siRNA targeting delivery
Abstract

Tumor-oriented nanocarrier drug delivery approaches with photosensitivity have drawn considerable attention over the years. However, due to its low penetrability and ability to harm tissues, the use of UV light for triggered nanocarrier release in in vivo applications has been limited. Compared with UV light, near-infrared (NIR) light deeply penetrates tissues and is less damaging to cells. In this study, we devised and tested a strategy for functional siRNA delivery to cells by loading siRNA into cationic liposomes bearing a photolabile-caged cell-penetrating peptide (pcCPP) and asparagine-glycine-arginine peptide (NGR) molecules attached to the liposome surface (pcCPP/NGR-LP). Here, the positive charges of the lysine residues on the CPP were temporarily caged by the photosensitive group (PG), neutralizing its charges and thereby forming a pcCPP. This event subsequently led to conditional NIR light-dependent cell-penetrating functionality. After administration, the pcCPP/NRG-LP was inactivated in the circulatory system as it could not penetrate the tumor cell membrane. The NGR moiety selectively bound to CD13-positive tumors, which facilitated the active accumulation of pcCPP/NGR-LP in tumor tissues. Then, upon illumination using NIR light at the tumor site, the PG was uncaged, the interaction of the CPP with the cell membrane was restored and the activated dual-modified liposomes exhibited enhanced tumor cellular uptake and selectivity due to the synergistic effect of CPP-mediated cellular entry and NGR-mediated endocytosis. Subsequent research demonstrated that the pcCPP/NGR-LP showed good physicochemical properties, effective cellular uptake, endosomal escape and significant gene silencing in HT-1080 cells in vitro. Additionally, after systemic administration in mice, pcCPP/NGR-LP accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the combined application of these pcCPP and NGR modifications may provide a reasonable approach for the selectively targeted delivery of siRNA.

Keywords
Near-infrared (NIR) two-photon photolysis; NGR-targeted; Cell-penetrating peptides; Small interfering RNA
First Page Preview
Dual-modified liposomes with a two-photon-sensitive cell penetrating peptide and NGR ligand for siRNA targeting delivery
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 48, April 2015, Pages 84–96
Authors
, , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us