Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles
RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA). To maintain a high level of growth, tumor cells scavenge h...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2011-04-01
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Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558611800126 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mian M.K. Shahzad Lingegowda S. Mangala Hee Dong Han Chunhua Lu Justin Bottsford-Miller Masato Nishimura Edna M. Mora Jeong-Won Lee Rebecca L. Stone Chad V. Pecot Duangmani Thanapprapasr Ju-Won Roh Puja Gaur Maya P. Nair Yun-Yong Park Nirupama Sabnis Michael T. Deavers Ju-Seog Lee Lee M. Ellis Gabriel Lopez-Berestein Walter J. McConathy Laszlo Prokai Andras G. Lacko Anil K. Sood |
spellingShingle |
Mian M.K. Shahzad Lingegowda S. Mangala Hee Dong Han Chunhua Lu Justin Bottsford-Miller Masato Nishimura Edna M. Mora Jeong-Won Lee Rebecca L. Stone Chad V. Pecot Duangmani Thanapprapasr Ju-Won Roh Puja Gaur Maya P. Nair Yun-Yong Park Nirupama Sabnis Michael T. Deavers Ju-Seog Lee Lee M. Ellis Gabriel Lopez-Berestein Walter J. McConathy Laszlo Prokai Andras G. Lacko Anil K. Sood Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles Neoplasia: An International Journal for Oncology Research |
author_facet |
Mian M.K. Shahzad Lingegowda S. Mangala Hee Dong Han Chunhua Lu Justin Bottsford-Miller Masato Nishimura Edna M. Mora Jeong-Won Lee Rebecca L. Stone Chad V. Pecot Duangmani Thanapprapasr Ju-Won Roh Puja Gaur Maya P. Nair Yun-Yong Park Nirupama Sabnis Michael T. Deavers Ju-Seog Lee Lee M. Ellis Gabriel Lopez-Berestein Walter J. McConathy Laszlo Prokai Andras G. Lacko Anil K. Sood |
author_sort |
Mian M.K. Shahzad |
title |
Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles |
title_short |
Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles |
title_full |
Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles |
title_fullStr |
Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles |
title_full_unstemmed |
Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles |
title_sort |
targeted delivery of small interfering rna using reconstituted high-density lipoprotein nanoparticles |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2011-04-01 |
description |
RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA). To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL) particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1). In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and established a novel formulation of siRNA by incorporating it into reconstituted HDL (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase) in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore, this novel technology could serve as the foundation for new cancer therapeutic approaches.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558611800126 |
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doaj-d2b1e57fbc9c4c7d8cb4be4b81ac9da42020-11-25T01:08:04ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-04-0113430931910.1593/neo.101372Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein NanoparticlesMian M.K. Shahzad0Lingegowda S. Mangala1Hee Dong Han2Chunhua Lu3Justin Bottsford-Miller4Masato Nishimura5Edna M. Mora6Jeong-Won Lee7Rebecca L. Stone8Chad V. Pecot9Duangmani Thanapprapasr10Ju-Won Roh11Puja Gaur12Maya P. Nair13Yun-Yong Park14Nirupama Sabnis15Michael T. Deavers16Ju-Seog Lee17Lee M. Ellis18Gabriel Lopez-Berestein19Walter J. McConathy20Laszlo Prokai21Andras G. Lacko22Anil K. Sood23Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Radiation Biophysics, NASA Johnson Space Center, University of Space Research Association, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Molecular Biology & Immunology, University of North Texas-HSC, Fort Worth, TX, USADepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Molecular Biology & Immunology, University of North Texas-HSC, Fort Worth, TX, USADepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Internal Medicine, Texas Tech University-HSC, Fort Worth, TX, USADepartment of Molecular Biology & Immunology, University of North Texas-HSC, Fort Worth, TX, USADepartment of Molecular Biology & Immunology, University of North Texas-HSC, Fort Worth, TX, USADepartment of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA). To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL) particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1). In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and established a novel formulation of siRNA by incorporating it into reconstituted HDL (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase) in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore, this novel technology could serve as the foundation for new cancer therapeutic approaches. http://www.sciencedirect.com/science/article/pii/S1476558611800126 |