Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer
Abstract Delivery of nucleic acids into solid tumor environments remains a pressing challenge. This study examines the ability of macrophages to horizontally transfer small interfering RNA (siRNA) lipoplexes to cancer cells. Macrophages are a natural candidate for a drug carrier because of their abi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.201900582 |
| _version_ | 1818504134731497472 |
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| author | Elizabeth C. Wayne Christian Long Matthew J. Haney Elena V. Batrakova Tina M. Leisner Leslie V. Parise Alexander V. Kabanov |
| author_facet | Elizabeth C. Wayne Christian Long Matthew J. Haney Elena V. Batrakova Tina M. Leisner Leslie V. Parise Alexander V. Kabanov |
| author_sort | Elizabeth C. Wayne |
| collection | DOAJ |
| description | Abstract Delivery of nucleic acids into solid tumor environments remains a pressing challenge. This study examines the ability of macrophages to horizontally transfer small interfering RNA (siRNA) lipoplexes to cancer cells. Macrophages are a natural candidate for a drug carrier because of their ability to accumulate at high densities into many cancer types, including, breast, prostate, brain, and colon cancer. Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture. The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered. Macrophages loaded with calcium integrin binding protein‐1 (CIB1)‐siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA‐MB‐468 human breast cancer cells. Adoptive transfer of macrophages transfected with CIB1‐siRNA localizes to the orthotopic MDA‐MB‐468 tumor. Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a. As macrophages are heavily involved in tumor progression, understanding how to use macrophages for drug delivery can substantially benefit the treatment of tumors. |
| first_indexed | 2024-12-10T21:33:04Z |
| format | Article |
| id | doaj.art-588c1ca743bb4fdf881e4c3a28d78148 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-10T21:33:04Z |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-588c1ca743bb4fdf881e4c3a28d781482022-12-22T01:32:43ZengWileyAdvanced Science2198-38442019-11-01621n/an/a10.1002/advs.201900582Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene TransferElizabeth C. Wayne0Christian Long1Matthew J. Haney2Elena V. Batrakova3Tina M. Leisner4Leslie V. Parise5Alexander V. Kabanov6Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmacuetics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACenter for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmacuetics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACenter for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmacuetics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACenter for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmacuetics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USABiochemistry and Biophysics University of North Carolina at Chapel Hill Chapel Hill NC 27599 USABiochemistry and Biophysics University of North Carolina at Chapel Hill Chapel Hill NC 27599 USACenter for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmacuetics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USAAbstract Delivery of nucleic acids into solid tumor environments remains a pressing challenge. This study examines the ability of macrophages to horizontally transfer small interfering RNA (siRNA) lipoplexes to cancer cells. Macrophages are a natural candidate for a drug carrier because of their ability to accumulate at high densities into many cancer types, including, breast, prostate, brain, and colon cancer. Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture. The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered. Macrophages loaded with calcium integrin binding protein‐1 (CIB1)‐siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA‐MB‐468 human breast cancer cells. Adoptive transfer of macrophages transfected with CIB1‐siRNA localizes to the orthotopic MDA‐MB‐468 tumor. Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a. As macrophages are heavily involved in tumor progression, understanding how to use macrophages for drug delivery can substantially benefit the treatment of tumors.https://doi.org/10.1002/advs.201900582cancergene deliveryimmunotherapymacrophagessmall interfering RNA (siRNA) |
| spellingShingle | Elizabeth C. Wayne Christian Long Matthew J. Haney Elena V. Batrakova Tina M. Leisner Leslie V. Parise Alexander V. Kabanov Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer Advanced Science cancer gene delivery immunotherapy macrophages small interfering RNA (siRNA) |
| title | Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer |
| title_full | Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer |
| title_fullStr | Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer |
| title_full_unstemmed | Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer |
| title_short | Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer |
| title_sort | targeted delivery of sirna lipoplexes to cancer cells using macrophage transient horizontal gene transfer |
| topic | cancer gene delivery immunotherapy macrophages small interfering RNA (siRNA) |
| url | https://doi.org/10.1002/advs.201900582 |
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