Designed ferritin nanocages displaying trimeric TRAIL and tumor-targeting peptides confer superior anti-tumor efficacy

Scientific Reports
Jae Do YooSoyoun Kim

Abstract

TRAIL is considered a promising target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors, DR4 or DR5. Although recombinant human TRAIL has shown high potency and specificity for killing cancer cells in preclinical studies, it has failed in multiple clinical trials for several reasons, including a very short half-life mainly caused by instability of the monomeric form of TRAIL and rapid renal clearance of the off-targeted TRAIL. To overcome such obstacles, we developed a TRAIL-active trimer nanocage (TRAIL-ATNC) that presents the TRAIL ligand in its trimer-like conformation by connecting it to a triple helix sequence that links to the threefold axis of the ferritin nanocage. We also ligated the tumor-targeting peptide, IL4rP, to TRAIL-ATNC to enhance tumor targeting. The developed TRAIL-ATNCIL4rP showed enhanced agonistic activity compared with monomeric TRAIL. The in vivo serum half-life of TRAIL-ATNCIL4rP was ~ 16-times longer than that of native TRAIL. As a consequence of these properties, TRAIL-ATNCIL4rP exhibited efficacy as an anti-tumor agent in vivo against xenograft breast cancer as well as orthotopic pan...Continue Reading

References

Jun 1, 1994·Current Opinion in Immunology·R J Armitage
Jan 1, 1994·Clinical and Experimental Immunology·N I ObiriR K Puri
Jul 10, 1997·Nature·M IrmlerJ Tschopp
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Jun 6, 2003·Cytokine & Growth Factor Reviews·Alexandru Almasan, Avi Ashkenazi
Jun 10, 2005·Journal of Translational Medicine·Bonnie L HylanderElizabeth A Repasky
Apr 28, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tom M GantenHenning Walczak
May 13, 2006·Science·Trevor Douglas, Mark Young
Apr 17, 2008·Molecular Cancer Therapeutics·Lin CaoZi-Chun Hua
Jul 26, 2008·Nature Nanotechnology·Dan PeerRobert Langer
Sep 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wenhong RenDina Lev
Nov 18, 2008·Cellular and Molecular Life Sciences : CMLS·G ZauliP Secchiero
May 12, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Roy S HerbstDavid S Mendelson
Mar 10, 2011·Journal of the American Chemical Society·Elsa ValeroNatividad Gálvez
Nov 8, 2013·ACS Nano·Jong-Hwan LeeJeewon Lee
Nov 23, 2013·Nanomedicine : Nanotechnology, Biology, and Medicine·Jae-A HanSebyung Kang
Dec 4, 2013·Vaccine·Liang ZhaoAnton P J Middelberg
Jan 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michael J MitchellMichael R King
Jan 15, 2014·Cytokine & Growth Factor Reviews·Pamela M Holland
May 9, 2014·Nature Communications·Ran NamgungWon Jong Kim

❮ Previous
Next ❯

Citations

Nov 3, 2021·Nano Convergence·Jessica A Kemp, Young Jik Kwon

❮ Previous
Next ❯

Methods Mentioned

BETA
Transmission electron microscopy
dynamic
Light Scattering
fluorescence-activated cell sorting
flow cytometry
surface plasmon resonance
chips
xenograft
electrophoresis
Assay

Software Mentioned

Image J
PyMOL Graphics System
Living Image
Scrubber
PyMOL
GraphPad Prism

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis