Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study
Use of exogenous small interfering RNA (siRNA) has shown potential in gene silencing. The need for target-specific siRNA delivery vehicles is crucial to successful gene silencing. This study is aimed at developing and evaluating the safety and efficiency of siRNA delivery using unmodified and folic...
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| Format: | Article |
| Language: | English |
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Sciendo
2019-03-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2019-0008 |
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| author | Mbatha Londiwe Simphiwe Maiyo Fiona Chepkoech Singh Moganavelli |
| author_facet | Mbatha Londiwe Simphiwe Maiyo Fiona Chepkoech Singh Moganavelli |
| author_sort | Mbatha Londiwe Simphiwe |
| collection | DOAJ |
| description | Use of exogenous small interfering RNA (siRNA) has shown potential in gene silencing. The need for target-specific siRNA delivery vehicles is crucial to successful gene silencing. This study is aimed at developing and evaluating the safety and efficiency of siRNA delivery using unmodified and folic acid (FA) modified poly(amidoamine) generation 5 (PAMAM G5D) functionalized gold nanoparticles (Au:G5D/Au:G5D:FA) in vitro. All formulations were physico--chemically characterized and nanocomplexes were evaluated using the band shift, dye displacement, nuclease protection, MTT cell viability, and luciferase reporter gene assays. Nanocomplexes bound and protected siRNA against degrading RNases, and were well tolerated by the cells. The Au:G5D:FA nanocomplexes elicited excellent gene silencing in folate receptor expressing HeLa-Tat-Luc cells, decreasing significantly in the presence of excess FA ligand, indicating nanocomplex uptake by the mechanism of receptor mediation. These results highlight the synergistic role played by Au and the dendrimer in enhancement of transgene silencing. |
| format | Article |
| id | doaj-art-75264c7228af4c4887ef2d72113fe7cf |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-75264c7228af4c4887ef2d72113fe7cf2025-02-02T16:53:17ZengSciendoActa Pharmaceutica1846-95582019-03-01691496110.2478/acph-2019-0008acph-2019-0008Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle studyMbatha Londiwe Simphiwe0Maiyo Fiona Chepkoech1Singh Moganavelli2Non-Viral Delivery Laboratory Discipline of BiochemistryUniversity of KwaZulu-Natal Westville Campus, School of Life Sciences, Private Bag X54001, Durban4000South AfricaNon-Viral Delivery Laboratory Discipline of BiochemistryUniversity of KwaZulu-Natal Westville Campus, School of Life Sciences, Private Bag X54001, Durban4000South AfricaNon-Viral Delivery Laboratory Discipline of BiochemistryUniversity of KwaZulu-Natal Westville Campus, School of Life Sciences, Private Bag X54001, Durban4000South AfricaUse of exogenous small interfering RNA (siRNA) has shown potential in gene silencing. The need for target-specific siRNA delivery vehicles is crucial to successful gene silencing. This study is aimed at developing and evaluating the safety and efficiency of siRNA delivery using unmodified and folic acid (FA) modified poly(amidoamine) generation 5 (PAMAM G5D) functionalized gold nanoparticles (Au:G5D/Au:G5D:FA) in vitro. All formulations were physico--chemically characterized and nanocomplexes were evaluated using the band shift, dye displacement, nuclease protection, MTT cell viability, and luciferase reporter gene assays. Nanocomplexes bound and protected siRNA against degrading RNases, and were well tolerated by the cells. The Au:G5D:FA nanocomplexes elicited excellent gene silencing in folate receptor expressing HeLa-Tat-Luc cells, decreasing significantly in the presence of excess FA ligand, indicating nanocomplex uptake by the mechanism of receptor mediation. These results highlight the synergistic role played by Au and the dendrimer in enhancement of transgene silencing.https://doi.org/10.2478/acph-2019-0008sirnagold nanoparticlesdendrimersfolic acidgene silencing |
| spellingShingle | Mbatha Londiwe Simphiwe Maiyo Fiona Chepkoech Singh Moganavelli Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study Acta Pharmaceutica sirna gold nanoparticles dendrimers folic acid gene silencing |
| title | Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study |
| title_full | Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study |
| title_fullStr | Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study |
| title_full_unstemmed | Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study |
| title_short | Dendrimer functionalized folate-targeted gold nanoparticles for luciferase gene silencing in vitro: A proof of principle study |
| title_sort | dendrimer functionalized folate targeted gold nanoparticles for luciferase gene silencing in vitro a proof of principle study |
| topic | sirna gold nanoparticles dendrimers folic acid gene silencing |
| url | https://doi.org/10.2478/acph-2019-0008 |
| work_keys_str_mv | AT mbathalondiwesimphiwe dendrimerfunctionalizedfolatetargetedgoldnanoparticlesforluciferasegenesilencinginvitroaproofofprinciplestudy AT maiyofionachepkoech dendrimerfunctionalizedfolatetargetedgoldnanoparticlesforluciferasegenesilencinginvitroaproofofprinciplestudy AT singhmoganavelli dendrimerfunctionalizedfolatetargetedgoldnanoparticlesforluciferasegenesilencinginvitroaproofofprinciplestudy |