Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles

Author(s)
Su, Xingfang; Yang, Nicole Jie Yeon; Wittrup, Karl Dane; Irvine, Darrell J
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Abstract
Plant-derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells. We tested a concept for two-stage delivery, whereby tumor cells precoated with an antibody-targeted gelonin toxin were killed by exposure to endosome-disrupting polymer nanoparticles. Co-internalization of particles and tumor cell-bound gelonin led to cytosolic delivery and >50-fold enhancement of toxin efficacy. This approach allows the extreme potency of gelonin to be focused on tumors with significantly reduced potential for off-target toxicity.
Date issued
2013-04
URI
http://hdl.handle.net/1721.1/79767
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Ragon Institute of MGH, MIT and Harvard; Koch Institute for Integrative Cancer Research at MIT
Journal
Biomacromolecules
Publisher
American Chemical Society
Citation
Su, Xingfang, Nicole Yang, K. Dane Wittrup, and Darrell J. Irvine. Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles. Biomacromolecules 14, no. 4 (April 8, 2013): 1093-1102.
Version: Final published version
ISSN
1525-7797
1526-4602
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