SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression
Macrophage polarization has been shown to be a key event in inflammatory processes. It follows that manipulation of macrophage states may offer a powerful tool to control innate immune responses. In this project, we studied the use of Poly (lactic-co-glycolic acid) PLGA microspheres to deliver small...
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| Format: | Final Year Project (FYP) |
| Language: | English |
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2015
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| Online Access: | http://hdl.handle.net/10356/65233 |
| _version_ | 1826115826273484800 |
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| author | Lin, Junquan |
| author2 | Chong Seow Khoon, Mark |
| author_facet | Chong Seow Khoon, Mark Lin, Junquan |
| author_sort | Lin, Junquan |
| collection | NTU |
| description | Macrophage polarization has been shown to be a key event in inflammatory processes. It follows that manipulation of macrophage states may offer a powerful tool to control innate immune responses. In this project, we studied the use of Poly (lactic-co-glycolic acid) PLGA microspheres to deliver small interfering RNA (siRNA) for post-transcriptional gene silencing for applications in engineering macrophage fates. Three human monocytic cell lines were selected to generate model macrophage populations; THP-1, U937 and HL60. Classical macrophage polarization protocols were applied to all three cell lines to generate M0, M1 and M2 phenotypes, and subsequently characterized by macrophage characteristics. In parallel, PLGA microspheres were engineered and characterized in their efficiency as drug delivery vehicles to macrophage lines. Finally, PLGA microspheres carrying siRNA against human TNF-α (siTNF) were incubated with polarized macrophage populations. This treatment was shown to be useful in attenuating TNF-α gene expression in all three cell lines, achieving 66.2%, 87.1% and 89% reduction in M1 polarized THP-1, U937 and HL60 cells respectively. Expression of selected markers was also evaluated as an indication of pro- and anti-inflammatory responses to siTNF treatment. In conclusion, the results suggest siRNA-loaded microspheres to be effective for the manipulation of macrophage states. Ongoing work includes studying the use of siRNA and therapeutic gene combinations to effect greater control of macrophage fate. |
| first_indexed | 2024-10-01T04:01:31Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/65233 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:01:31Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/652332023-03-03T15:34:21Z SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression Lin, Junquan Chong Seow Khoon, Mark School of Chemical and Biomedical Engineering DRNTU::Engineering::Bioengineering Macrophage polarization has been shown to be a key event in inflammatory processes. It follows that manipulation of macrophage states may offer a powerful tool to control innate immune responses. In this project, we studied the use of Poly (lactic-co-glycolic acid) PLGA microspheres to deliver small interfering RNA (siRNA) for post-transcriptional gene silencing for applications in engineering macrophage fates. Three human monocytic cell lines were selected to generate model macrophage populations; THP-1, U937 and HL60. Classical macrophage polarization protocols were applied to all three cell lines to generate M0, M1 and M2 phenotypes, and subsequently characterized by macrophage characteristics. In parallel, PLGA microspheres were engineered and characterized in their efficiency as drug delivery vehicles to macrophage lines. Finally, PLGA microspheres carrying siRNA against human TNF-α (siTNF) were incubated with polarized macrophage populations. This treatment was shown to be useful in attenuating TNF-α gene expression in all three cell lines, achieving 66.2%, 87.1% and 89% reduction in M1 polarized THP-1, U937 and HL60 cells respectively. Expression of selected markers was also evaluated as an indication of pro- and anti-inflammatory responses to siTNF treatment. In conclusion, the results suggest siRNA-loaded microspheres to be effective for the manipulation of macrophage states. Ongoing work includes studying the use of siRNA and therapeutic gene combinations to effect greater control of macrophage fate. Bachelor of Engineering (Chemical and Biomolecular Engineering) 2015-06-17T02:56:10Z 2015-06-17T02:56:10Z 2015 2015 Final Year Project (FYP) http://hdl.handle.net/10356/65233 en Nanyang Technological University 55 p. application/pdf |
| spellingShingle | DRNTU::Engineering::Bioengineering Lin, Junquan SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression |
| title | SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression |
| title_full | SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression |
| title_fullStr | SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression |
| title_full_unstemmed | SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression |
| title_short | SIRNA-loaded PLGA microspheres for regulation of macrophage gene expression |
| title_sort | sirna loaded plga microspheres for regulation of macrophage gene expression |
| topic | DRNTU::Engineering::Bioengineering |
| url | http://hdl.handle.net/10356/65233 |
| work_keys_str_mv | AT linjunquan sirnaloadedplgamicrospheresforregulationofmacrophagegeneexpression |