Improved antitumor activity of TRAIL fusion protein via formation of self-assembling nanoparticle.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been known as a promising agent for cancer therapy due to its specific apoptosis-inducing effect on tumor cells rather than most normal cells. However, systemically delivered TRAIL suffers from a rapid clearance from the body with an extremely short half-life. Thermally responsive elastin-like polypeptides (ELPs) are a promising class of temperature sensitive biopolymers based on the structural motif found in mammalian tropoelastin and retain the advantages of polymeric drug delivery systems. We therefore expressed RGD-TRAIL fused with ELP (RGD-TRAIL-ELP) in E. coli. Purification of RGD-TRAIL-ELP was achieved by the conveniently inverse transition cycling (ITC). The purified RGD-TRAIL-ELP without any chemical conjugation was able to self-assemble into nanoparticle under physiological condition. Non-reducing SDS-PAGE results showed that trimer content of RGD-TRAIL-ELP increased 3.4-fold than RGD-TRAIL. Flow cytometry confirmed that RGD-TRAIL-ELP 3-fold enhanced apoptosis-inducing capacity than RGD-TRAIL. Single intraperitoneal injection of the RGD-TRAIL-ELP nanoparticle induced nearly complete tumor regression in the COLO-205 tumor xenograft model. Histological observation confirmed that RGD-TRAIL-ELP induced significant tumor cell apoptosis without apparent liver toxicity. These findings suggested that a great potential application of the RGD-TRAIL-ELP nanoparticle system as a safe and efficient delivery strategy for cancer therapy.

• Authors: Kaizong Huang, Ningjun Duan, Chunmei Zhang, Ran Mo, Zichun Hua
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 41904 (02 22 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28225020 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Oligopeptides
• Recombinant Proteins
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• arginyl-glycyl-aspartic acid
• Elastin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Apoptosis
• Cell Line, Tumor
• Elastin (genetics)
• Female
• Humans
• Mice
• Mice, Nude
• Nanoparticles (chemistry)
• Neoplasms, Experimental (drug therapy)
• Oligopeptides (genetics)
• Recombinant Proteins (administration & dosage, genetics, therapeutic use)
• TNF-Related Apoptosis-Inducing Ligand (administration & dosage, genetics, therapeutic use)