Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
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-...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2013
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| Online Access: | http://hdl.handle.net/1721.1/79767 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-0882-7761 |
| _version_ | 1826196056637964288 |
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| author | Su, Xingfang Yang, Nicole Jie Yeon Wittrup, Karl Dane Irvine, Darrell J |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Su, Xingfang Yang, Nicole Jie Yeon Wittrup, Karl Dane Irvine, Darrell J |
| author_sort | Su, Xingfang |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:20:10Z |
| format | Article |
| id | mit-1721.1/79767 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:20:10Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/797672022-09-26T17:15:55Z Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles Su, Xingfang Yang, Nicole Jie Yeon Wittrup, Karl Dane Irvine, Darrell J 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 Su, Xingfang Yang, Nicole Jie Yeon Wittrup, Karl Dane Irvine, Darrell J. 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. United States. Dept. of Defense (Institute for Soldier Nanotechnology, contract W911NF-07-D-0004) Howard Hughes Medical Institute (Investigator) Singapore. Agency for Science, Technology and Research 2013-08-02T17:23:07Z 2013-08-02T17:23:07Z 2013-04 2013-02 Article http://purl.org/eprint/type/JournalArticle 1525-7797 1526-4602 http://hdl.handle.net/1721.1/79767 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. https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-0882-7761 en_US http://dx.doi.org/10.1021/bm3019906 Biomacromolecules Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society PMC |
| spellingShingle | Su, Xingfang Yang, Nicole Jie Yeon Wittrup, Karl Dane Irvine, Darrell J Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles |
| title | Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles |
| title_full | Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles |
| title_fullStr | Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles |
| title_full_unstemmed | Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles |
| title_short | Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles |
| title_sort | synergistic antitumor activity from two stage delivery of targeted toxins and endosome disrupting nanoparticles |
| url | http://hdl.handle.net/1721.1/79767 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-0882-7761 |
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