RNA-Peptide nanoplexes drug DNA damage pathways in high-grade serous ovarian tumors
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Dreaden_et_al-2018-Bioengineering_%26_Translational_Medicine.pdf
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1.46 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Dreaden, Erik
Kong, Yi Wen
Quadir, Mohiuddin Abdul
Correa Echavarria, Santiago
Suarez Lopez, Lucia
Barberio, Antonio Eric
Hwang, Mun Kyung
Shi, Aria C.
Oberlton, Benjamin J.
Gallagher, Paige N.
Date Issued
January 2018
Journal
Bioengineering & Translational Medicine
Publisher
Wiley
Citation
Dreaden, Erik C. et al. “RNA-Peptide Nanoplexes Drug DNA Damage Pathways in High-Grade Serous Ovarian Tumors.” Bioengineering & Translational Medicine 3, 1 (January 2018): 26–36 © 2018 The Authors
Version
Final published version
Abstract
DNA damaging chemotherapy is a cornerstone of current front‐line treatments for advanced ovarian cancer (OC). Despite the fact that a majority of these patients initially respond to therapy, most will relapse with chemo‐resistant disease; therefore, adjuvant treatments that synergize with DNA‐damaging chemotherapy could improve treatment outcomes and survival in patients with this deadly disease. Here, we report the development of a nanoscale peptide‐nucleic acid complex that facilitates tumor‐specific RNA interference therapy to chemosensitize advanced ovarian tumors to frontline platinum/taxane therapy. We found that the nanoplex‐mediated silencing of the protein kinase, MK2, profoundly sensitized mouse models of high‐grade serous OC to cytotoxic chemotherapy by blocking p38/MK2‐dependent cell cycle checkpoint maintenance. Combined RNAi therapy improved overall survival by 37% compared with platinum/taxane chemotherapy alone and decreased metastatic spread to the lungs without observable toxic side effects. These findings suggest (a) that peptide nanoplexes can serve as safe and effective delivery vectors for siRNA and (b) that combined inhibition of MK2 could improve treatment outcomes in patients currently receiving frontline chemotherapy for advanced OC.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1002/BTM2.10086
