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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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
2013-04Department
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 MITJournal
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