PEGylated TNF-related apoptosis-inducing ligand (TRAIL) for effective tumor combination therapy

Hai Hua Jiang, Tae Hyung Kim, Seulki Lee, Xiaoyuan Chen, Yu Seok Youn, Kang Choon Lee

Research output: Contribution to journalArticle

Abstract

Although PEGylated TNF-related apoptosis-inducing ligand (PEG-TRAIL) has good tumor cell specificity and stability, its therapeutic potential is restricted by the development of tumor cell resistance. The purpose of this study was to develop an effective combination therapy with sustained biological activity based on microspheres. Doxorubicin (DOX), PEG-TRAIL, and DOX plus PEG-TRAIL (dual agent) were microencapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres using a double-emulsion solvent extraction method. Prepared dual agent microspheres showed the encapsulation efficiency 69.4 ± 2.3 for DOX and 87.7 ± 2.9% for PEG-TRAIL. Potential anti-tumor efficacy of this system was investigated in vitro and in vivo in a human colon cancer (HCT116) and in a human prostate cancer (PC-3). DOX and PEG-TRAIL release from dual agent microspheres were biologically active and significantly inhibited the TRAIL-sensitive HCT116 and resistant PC-3 cells in vitro. Dual agent microspheres simultaneous delivery of DOX and PEG-TRAIL was superior to all other DOX or PEG-TRAIL microspheres in vivo. A single local injection of PLGA microspheres loaded with low amounts of DOX, PEG-TRAIL, or dual agent resulted in 14.8, 30.2, and 63.6% reductions in HCT116 tumor volume and 20.4, 14.2, and 67.7% reductions in PC-3 tumor volume at 35 days. Our findings show that dual agent microspheres offer a promising means of delivering DOX and PEG-TRAIL to tumor sites.

Original languageEnglish (US)
Pages (from-to)8529-8537
Number of pages9
JournalBiomaterials
Volume32
Issue number33
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

TNF-Related Apoptosis-Inducing Ligand
Cell death
Tumors
Microspheres
Doxorubicin
Ligands
Neoplasms
Therapeutics
Tumor Burden
Cells
Acids
Solvent extraction
Bioactivity
Emulsions
Encapsulation
Colonic Neoplasms
Prostatic Neoplasms

Keywords

  • Combination therapy
  • Doxorubicin
  • Microspheres
  • PEG-TRAIL
  • Sequential delivery

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

PEGylated TNF-related apoptosis-inducing ligand (TRAIL) for effective tumor combination therapy. / Jiang, Hai Hua; Kim, Tae Hyung; Lee, Seulki; Chen, Xiaoyuan; Youn, Yu Seok; Lee, Kang Choon.

In: Biomaterials, Vol. 32, No. 33, 11.2011, p. 8529-8537.

Research output: Contribution to journalArticle

Jiang, Hai Hua ; Kim, Tae Hyung ; Lee, Seulki ; Chen, Xiaoyuan ; Youn, Yu Seok ; Lee, Kang Choon. / PEGylated TNF-related apoptosis-inducing ligand (TRAIL) for effective tumor combination therapy. In: Biomaterials. 2011 ; Vol. 32, No. 33. pp. 8529-8537.
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