期刊
BIOMATERIALS
卷 32, 期 13, 页码 3538-3546出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.01.054
关键词
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); Polyethylene glycol (PEG); Nanoparticle protein/peptide drug delivery
资金
- Korean Ministry of Education, Science, and Technology [2010K001256]
TRAIL has received considerable attention as a potential anti-cancer agent due to its specific ability to target tumors. However, recombinant TRAIL has several limitations, such as, its short biological half-life, its inherent instability, and its potential hepatotoxicity. In this study, we developed a sustained release nanoparticle formulation of TRAIL and investigated its therapeutic effects in tumor-bearing mice. TRAIL-loaded nanoparticles (NPs) were prepared by mixing PEGylated heparin (PEG-HE), poly-L-lysine (PLL). and TRAIL NPs prepared by the ionic interaction between polymer and TRAIL showed uniform spherical structures of diameter 213.3 +/- 9.7 nm and a surface charge of 5.33 +/- 1.2 mV. An in vitro study of the bioactivity of TRAIL in NPs showed that TRAIL-loaded PEG-HE/PL. NPs (TRAIL-PEG-NPs) were slightly less cytotoxic than TRAIL in vitro. To investigate pharmacokinetic parameters, TRAIL and TRAIL-PEG-NPs were intravenously injected into SD rats. The PEG-NP-based formulation demonstrated a 28.3 fold greater half-life than TRAIL alone. To evaluate the anti-tumor effect, TRAIL TRAIL-loaded HE/PLL NPs (TRAIL-NPs), and TRAIL-PEG-NPs were intravenously injected into HCT-116 tumor-bearing BALB/c athymic mice. The TRAIL-PEG-NP formulation efficiently suppressed tumor growth (>70%), and histological findings confirmed that NPs induced significant tumor cell apoptosis without inducing liver toxicity. The PEG-exposed NP fabrication method applied in this study could be widely applied to protein and peptide delivery systems. (C) 2011 Elsevier Ltd. All rights reserved.
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