Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles
Short interfering RNA (siRNA) targeted against anti-apoptotic Bcl-2 protein proved to knockdown its expression and trigger cancer cell death. We used degradable, pH-sensitive, comb-like [P(EAA-co-BMA)-b-PNASI-g-P(HMA-co-TMAEMA)] polymer to condense anti-Bcl-2 siRNA into “smart” particles, which prov...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-09-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | http://www.mdpi.com/2079-4983/5/3/167 |
| _version_ | 1811187120145956864 |
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| author | Yen-Ling Lin Guohua Jiang Zhaocheng Zhang Jacques E. Nör Mohamed E. H. ElSayed |
| author_facet | Yen-Ling Lin Guohua Jiang Zhaocheng Zhang Jacques E. Nör Mohamed E. H. ElSayed |
| author_sort | Yen-Ling Lin |
| collection | DOAJ |
| description | Short interfering RNA (siRNA) targeted against anti-apoptotic Bcl-2 protein proved to knockdown its expression and trigger cancer cell death. We used degradable, pH-sensitive, comb-like [P(EAA-co-BMA)-b-PNASI-g-P(HMA-co-TMAEMA)] polymer to condense anti-Bcl-2 siRNA into “smart” particles, which proved to shuttle their cargo past the endosomal membrane and into the cytoplasm of HeLa and UM-SCC-17B cancer cells. HeLa and UM-SCC-17B cancer cells were treated with anti-Bcl-2 particles followed by quantifying Bcl-2 mRNA and protein levels using qRT-PCR and western blotting, respectively. “Smart” anti-Bcl-2 particles selectively suppress Bcl-2 mRNA and protein levels in HeLa cells by 50%–60% and 79%–81%, respectively. Similarly, “smart” anti-Bcl-2 particles inhibited Bcl-2 mRNA levels by 30%, 40%, and 20% upon incubation with UM-SCC-17B cancer cells for 48, 72, and 96 h, respectively. Bcl-2 protein expression in UM-SCC-17B cancer cells was inhibited by 30% after treatment for 72 h. Results show that pH-sensitive comb-like polymer complex anti-Bcl-2 siRNA forming “smart” nanoparticles that deliver their cargo into the cytoplasm of HeLa and UM-SCC-17B cancer cells causing Bcl-2 knockdown at the mRNA and protein levels. |
| first_indexed | 2024-04-11T13:56:51Z |
| format | Article |
| id | doaj.art-22f5e684cf8b4983b703ecffb0669652 |
| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-04-11T13:56:51Z |
| publishDate | 2014-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-22f5e684cf8b4983b703ecffb06696522022-12-22T04:20:13ZengMDPI AGJournal of Functional Biomaterials2079-49832014-09-015316718210.3390/jfb5030167jfb5030167Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” ParticlesYen-Ling Lin0Guohua Jiang1Zhaocheng Zhang2Jacques E. Nör3Mohamed E. H. ElSayed4Department of Biomedical Engineering, University of Michigan, 1101 Beal Ave., Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, 1101 Beal Ave., Ann Arbor, MI 48109, USADepartment of Cariology, Restorative Sciences, and Endodontics, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109, USADepartment of Cariology, Restorative Sciences, and Endodontics, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, 1101 Beal Ave., Ann Arbor, MI 48109, USAShort interfering RNA (siRNA) targeted against anti-apoptotic Bcl-2 protein proved to knockdown its expression and trigger cancer cell death. We used degradable, pH-sensitive, comb-like [P(EAA-co-BMA)-b-PNASI-g-P(HMA-co-TMAEMA)] polymer to condense anti-Bcl-2 siRNA into “smart” particles, which proved to shuttle their cargo past the endosomal membrane and into the cytoplasm of HeLa and UM-SCC-17B cancer cells. HeLa and UM-SCC-17B cancer cells were treated with anti-Bcl-2 particles followed by quantifying Bcl-2 mRNA and protein levels using qRT-PCR and western blotting, respectively. “Smart” anti-Bcl-2 particles selectively suppress Bcl-2 mRNA and protein levels in HeLa cells by 50%–60% and 79%–81%, respectively. Similarly, “smart” anti-Bcl-2 particles inhibited Bcl-2 mRNA levels by 30%, 40%, and 20% upon incubation with UM-SCC-17B cancer cells for 48, 72, and 96 h, respectively. Bcl-2 protein expression in UM-SCC-17B cancer cells was inhibited by 30% after treatment for 72 h. Results show that pH-sensitive comb-like polymer complex anti-Bcl-2 siRNA forming “smart” nanoparticles that deliver their cargo into the cytoplasm of HeLa and UM-SCC-17B cancer cells causing Bcl-2 knockdown at the mRNA and protein levels.http://www.mdpi.com/2079-4983/5/3/167pH-sensitive comb-like polymerssmart particlesendosomal escapecytoplasmic siRNA deliveryBcl-2 knockdown |
| spellingShingle | Yen-Ling Lin Guohua Jiang Zhaocheng Zhang Jacques E. Nör Mohamed E. H. ElSayed Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles Journal of Functional Biomaterials pH-sensitive comb-like polymers smart particles endosomal escape cytoplasmic siRNA delivery Bcl-2 knockdown |
| title | Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles |
| title_full | Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles |
| title_fullStr | Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles |
| title_full_unstemmed | Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles |
| title_short | Silencing Bcl-2 Expression in Epithelial Cancer Cells Using “Smart” Particles |
| title_sort | silencing bcl 2 expression in epithelial cancer cells using smart particles |
| topic | pH-sensitive comb-like polymers smart particles endosomal escape cytoplasmic siRNA delivery Bcl-2 knockdown |
| url | http://www.mdpi.com/2079-4983/5/3/167 |
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