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/PLL 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.