| dc.contributor |
Massachusetts Institute of Technology. Department of Chemical Engineering |
|
| dc.contributor |
Koch Institute for Integrative Cancer Research at MIT |
|
| dc.contributor |
Deng, Zhou J. |
|
| dc.contributor |
Morton, Stephen Winford |
|
| dc.contributor |
Ben-Akiva, Elana |
|
| dc.contributor |
Dreaden, Erik Christopher |
|
| dc.contributor |
Shopsowitz, Kevin |
|
| dc.contributor |
Hammond, Paula T. |
|
| dc.creator |
Deng, Zhou J. |
|
| dc.creator |
Morton, Stephen Winford |
|
| dc.creator |
Ben-Akiva, Elana |
|
| dc.creator |
Shopsowitz, Kevin |
|
| dc.creator |
Hammond, Paula T |
|
| dc.creator |
Dreaden, Erik |
|
| dc.date |
2016-02-12T20:55:37Z |
|
| dc.date |
2016-02-12T20:55:37Z |
|
| dc.date |
2013-10 |
|
| dc.date |
2013-08 |
|
| dc.date.accessioned |
2023-03-01T18:11:23Z |
|
| dc.date.available |
2023-03-01T18:11:23Z |
|
| dc.identifier |
1936-0851 |
|
| dc.identifier |
1936-086X |
|
| dc.identifier |
http://hdl.handle.net/1721.1/101180 |
|
| dc.identifier |
Deng, Zhou J., Stephen W. Morton, Elana Ben-Akiva, Erik C. Dreaden, Kevin E. Shopsowitz, and Paula T. Hammond. “Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment.” ACS Nano 7, no. 11 (November 26, 2013): 9571–9584. |
|
| dc.identifier |
https://orcid.org/0000-0002-4954-8443 |
|
| dc.identifier |
https://orcid.org/0000-0003-3988-0837 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/279088 |
|
| dc.description |
A single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-negative breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-l-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA molecules, and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose via intravenous administration significantly reduced the target gene expression in the tumors by almost 80%. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold in vitro and led to up to an 8-fold decrease in tumor volume compared to the control treatments with no observed toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system. |
|
| dc.description |
Janssen Pharmaceutical Ltd. (TRANSCEND Grant) |
|
| dc.description |
National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) |
|
| dc.description |
National Health and Medical Research Council (Australia) (CJ Martin Fellowship) |
|
| dc.description |
National Science Foundation (U.S.). Graduate Research Fellowship |
|
| dc.description |
Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship) |
|
| dc.format |
application/pdf |
|
| dc.language |
en_US |
|
| dc.publisher |
American Chemical Society (ACS) |
|
| dc.relation |
http://dx.doi.org/10.1021/nn4047925 |
|
| dc.relation |
ACS Nano |
|
| dc.rights |
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. |
|
| dc.source |
PMC |
|
| dc.title |
Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment |
|
| dc.type |
Article |
|
| dc.type |
http://purl.org/eprint/type/JournalArticle |
|