Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer
Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly...
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/113634 https://orcid.org/0000-0001-5088-5810 https://orcid.org/0000-0003-3383-0118 https://orcid.org/0000-0002-2515-5602 |
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| author | Lauffer, Sam Matulonis, Ursula Pepin, David Birrer, Michael J. Qi, Ruogu Wang, Yongheng Bruno, Peter Michael Xiao, Haihua Yu, Yingjie Li, Ting Chen, Qixian Kang, Xiang Song, Haiqin Yang, Xi Huang, Xing Detappe, Alexandre Hemann, Michael Ghoroghchian, Paiman Peter Wei, Wei, S.M. Massachusetts Institute of Technology. Department of Civil and Environmental Engineering |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Lauffer, Sam Matulonis, Ursula Pepin, David Birrer, Michael J. Qi, Ruogu Wang, Yongheng Bruno, Peter Michael Xiao, Haihua Yu, Yingjie Li, Ting Chen, Qixian Kang, Xiang Song, Haiqin Yang, Xi Huang, Xing Detappe, Alexandre Hemann, Michael Ghoroghchian, Paiman Peter Wei, Wei, S.M. Massachusetts Institute of Technology. Department of Civil and Environmental Engineering |
| author_sort | Lauffer, Sam |
| collection | MIT |
| description | Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly increase loading on a per-vehicle basis as compared to antibody-drug conjugates (ADCs). Their intraperitoneal administration enabled triggered release of the active MMAE toxin to inhibit tumor growth and to extend animal survival to > 90 days in a cell-line xenograft model of disseminated ovarian cancer. In a patient-derived xenograft model of advanced-stage and platinum-resistant ovarian cancer, an MMAE-based NDC doubled the duration of tumor growth inhibition as compared to cisplatin. NDCs of highly potent toxins thus introduce a translatable platform that may be exploited to maximize the safety and efficacy of cytotoxic chemotherapies, combining the best features of ADCs with those of nanoparticle-based therapeutics. |
| first_indexed | 2024-09-23T11:17:16Z |
| format | Article |
| id | mit-1721.1/113634 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:17:16Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1136342022-09-27T18:28:07Z Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer Lauffer, Sam Matulonis, Ursula Pepin, David Birrer, Michael J. Qi, Ruogu Wang, Yongheng Bruno, Peter Michael Xiao, Haihua Yu, Yingjie Li, Ting Chen, Qixian Kang, Xiang Song, Haiqin Yang, Xi Huang, Xing Detappe, Alexandre Hemann, Michael Ghoroghchian, Paiman Peter Wei, Wei, S.M. Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Koch Institute for Integrative Cancer Research at MIT Qi, Ruogu Wang, Yongheng Bruno, Peter Michael Xiao, Haihua Yu, Yingjie Li, Ting Chen, Qixian Kang, Xiang Song, Haiqin Yang, Xi Huang, Xing Detappe, Alexandre Hemann, Michael Ghoroghchian, Paiman Peter Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly increase loading on a per-vehicle basis as compared to antibody-drug conjugates (ADCs). Their intraperitoneal administration enabled triggered release of the active MMAE toxin to inhibit tumor growth and to extend animal survival to > 90 days in a cell-line xenograft model of disseminated ovarian cancer. In a patient-derived xenograft model of advanced-stage and platinum-resistant ovarian cancer, an MMAE-based NDC doubled the duration of tumor growth inhibition as compared to cisplatin. NDCs of highly potent toxins thus introduce a translatable platform that may be exploited to maximize the safety and efficacy of cytotoxic chemotherapies, combining the best features of ADCs with those of nanoparticle-based therapeutics. 2018-02-13T19:08:37Z 2018-02-13T19:08:37Z 2017-12 2017-09 2018-02-09T14:51:25Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/113634 Qi, Ruogu et al. “Nanoparticle Conjugates of a Highly Potent Toxin Enhance Safety and Circumvent Platinum Resistance in Ovarian Cancer.” Nature Communications 8, 1 (December 2017): 2166 © 2017 The Author(s) https://orcid.org/0000-0001-5088-5810 https://orcid.org/0000-0003-3383-0118 https://orcid.org/0000-0002-2515-5602 http://dx.doi.org/10.1038/s41467-017-02390-7 Nature Communications Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group |
| spellingShingle | Lauffer, Sam Matulonis, Ursula Pepin, David Birrer, Michael J. Qi, Ruogu Wang, Yongheng Bruno, Peter Michael Xiao, Haihua Yu, Yingjie Li, Ting Chen, Qixian Kang, Xiang Song, Haiqin Yang, Xi Huang, Xing Detappe, Alexandre Hemann, Michael Ghoroghchian, Paiman Peter Wei, Wei, S.M. Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| title | Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| title_full | Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| title_fullStr | Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| title_full_unstemmed | Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| title_short | Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| title_sort | nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer |
| url | http://hdl.handle.net/1721.1/113634 https://orcid.org/0000-0001-5088-5810 https://orcid.org/0000-0003-3383-0118 https://orcid.org/0000-0002-2515-5602 |
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