Merck
  • Home
  • Search Results
  • Dual-modified liposomes with a two-photon-sensitive cell penetrating peptide and NGR ligand for siRNA targeting delivery.

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

Biomaterials (2015-02-24)
Yang Yang, YanFang Yang, XiangYang Xie, ZhiYuan Wang, Wei Gong, Hui Zhang, Ying Li, FangLin Yu, ZhiPing Li, XingGuo Mei
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium orthovanadate, 99.98% trace metals basis
Sigma-Aldrich
Triethylamine, for amino acid analysis, ≥99.5% (GC)
Sigma-Aldrich
Triethylamine, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Triethylamine, puriss. p.a., ≥99.5% (GC)
Sigma-Aldrich
Triethylamine, for protein sequence analysis, ampule, ≥99.5% (GC)
Sigma-Aldrich
Triethylamine, ≥99.5%
Sigma-Aldrich
Sodium pyrophosphate tetrabasic, ≥95%
Sigma-Aldrich
Sodium orthovanadate, ≥90% (titration)
Sigma-Aldrich
Triethylamine, ≥99%
Sigma-Aldrich
Cholesteryl N-(2-dimethylaminoethyl)carbamate, ≥98% (TLC)
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
Cholesterol, from sheep wool, ≥92.5% (GC), powder
Supelco
Triethylamine, analytical standard
SAFC
Cholesterol, from sheep wool, Controlled origin, meets USP/NF testing specifications
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Sigma-Aldrich
Triethylamine, ≥99.5%
Supelco
Cholesterol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Supelco
Dichloromethane, Selectophore, ≥99.5%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)