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

• Main Authors: Su, Xingfang (Contributor), Yang, Nicole Jie Yeon (Contributor), Wittrup, Karl Dane (Contributor), Irvine, Darrell J (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Materials Science and Engineering (Contributor), Ragon Institute of MGH, MIT and Harvard (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Irvine, Darrell J. (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society, 2013-08-02T17:23:07Z.
• Subjects: Article
• Online Access: Get fulltext

 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.