Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells
Li Deng,1,* Yingying Zhang,1,* Lulu Ma,1,5,* Xiaolong Jing,1,3 Xingfa Ke,1,3 Jianhao Lian,1,3 Qiang Zhao,1,3 Bo Yan,1,3 Jinfeng Zhang,4 Jianzhong Yao,2 Jianming Chen1 1Department of Pharmaceutical Science, 2Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Sh...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/b6e5d2172e6d4695a10c50378a6df3fa |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:b6e5d2172e6d4695a10c50378a6df3fa |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:b6e5d2172e6d4695a10c50378a6df3fa2021-12-02T07:37:56ZComparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells1176-91141178-2013https://doaj.org/article/b6e5d2172e6d4695a10c50378a6df3fa2013-08-01T00:00:00Zhttp://www.dovepress.com/comparison-of-anti-egfr-fabrsquo-conjugated-immunoliposomes-modified-w-a14149https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Li Deng,1,* Yingying Zhang,1,* Lulu Ma,1,5,* Xiaolong Jing,1,3 Xingfa Ke,1,3 Jianhao Lian,1,3 Qiang Zhao,1,3 Bo Yan,1,3 Jinfeng Zhang,4 Jianzhong Yao,2 Jianming Chen1 1Department of Pharmaceutical Science, 2Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People’s Republic of China; 4Shanghai TCM Integrated Hospital, Shanghai, People’s Republic of China; 5Department of Pharmacy, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China *These authors contributed equally to this paper Background: Targeted liposome-polycation-DNA complex (LPD), mainly conjugated with antibodies using functionalized PEG derivatives, is an effective nanovector for systemic delivery of small interference RNA (siRNA). However, there are few studies reporting the effect of different conjugation linkers on LPD for gene silencing. To clarify the influence of antibody conjugation linkers on LPD, we prepared two different immunoliposomes to deliver siRNA in which DSPE-PEG-COOH and DSPE-PEG-MAL, the commonly used PEG derivative linkers, were used to conjugate anti-EGFR Fab’ with the liposome. Methods: First, 600 µg of anti-EGFR Fab’ was conjugated with 28.35 µL of a micelle solution containing DSPE-PEG-MAL or DSPE-PEG-COOH, and then post inserted into the prepared LPD. Various liposome parameters, including particle size, zeta potential, stability, and encapsulation efficiency were evaluated, and the targeting ability and gene silencing activity of TLPD-FPC (DSPE-PEG-COOH conjugated with Fab’) was compared with that of TLPD-FPM (DSPE-PEG-MAL conjugated with Fab’) in SMMC-7721 hepatocellular carcinoma cells. Results: There was no significant difference in particle size between the two TLPDs, but the zeta potential was significantly different. Further, although there was no significant difference in siRNA encapsulation efficiency, cell viability, or serum stability between TLPD-FPM and TLPD-FPC, cellular uptake of TLPD-FPM was significantly greater than that of TLPD-FPC in EGFR-overexpressing SMMC-7721 cells. The luciferase gene silencing efficiency of TLPD-FPM was approximately three-fold high than that of TLPD-FPC. Conclusion: Different conjugation linkers whereby antibodies are conjugated with LPD can affect the physicochemical properties of LPD and antibody conjugation efficiency, thus directly affecting the gene silencing effect of TLPD. Immunoliposomes prepared by DSPE-PEG-MAL conjugation with anti-EGFR Fab’ are more effective than TLPD containing DSPE-PEG-COOH in targeting hepatocellular carcinoma cells for siRNA delivery. Keywords: liposome-polycation-DNA, anti-EGFR Fab’, immunoliposomes, small interfering RNA delivery, conjugation technology, hepatocellular carcinomaDeng LZhang YMa LJing XKe XLian JZhao QYan BZhang JYao JChen JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 3271-3283 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Deng L Zhang Y Ma L Jing X Ke X Lian J Zhao Q Yan B Zhang J Yao J Chen J Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells |
| description |
Li Deng,1,* Yingying Zhang,1,* Lulu Ma,1,5,* Xiaolong Jing,1,3 Xingfa Ke,1,3 Jianhao Lian,1,3 Qiang Zhao,1,3 Bo Yan,1,3 Jinfeng Zhang,4 Jianzhong Yao,2 Jianming Chen1 1Department of Pharmaceutical Science, 2Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People’s Republic of China; 4Shanghai TCM Integrated Hospital, Shanghai, People’s Republic of China; 5Department of Pharmacy, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China *These authors contributed equally to this paper Background: Targeted liposome-polycation-DNA complex (LPD), mainly conjugated with antibodies using functionalized PEG derivatives, is an effective nanovector for systemic delivery of small interference RNA (siRNA). However, there are few studies reporting the effect of different conjugation linkers on LPD for gene silencing. To clarify the influence of antibody conjugation linkers on LPD, we prepared two different immunoliposomes to deliver siRNA in which DSPE-PEG-COOH and DSPE-PEG-MAL, the commonly used PEG derivative linkers, were used to conjugate anti-EGFR Fab’ with the liposome. Methods: First, 600 µg of anti-EGFR Fab’ was conjugated with 28.35 µL of a micelle solution containing DSPE-PEG-MAL or DSPE-PEG-COOH, and then post inserted into the prepared LPD. Various liposome parameters, including particle size, zeta potential, stability, and encapsulation efficiency were evaluated, and the targeting ability and gene silencing activity of TLPD-FPC (DSPE-PEG-COOH conjugated with Fab’) was compared with that of TLPD-FPM (DSPE-PEG-MAL conjugated with Fab’) in SMMC-7721 hepatocellular carcinoma cells. Results: There was no significant difference in particle size between the two TLPDs, but the zeta potential was significantly different. Further, although there was no significant difference in siRNA encapsulation efficiency, cell viability, or serum stability between TLPD-FPM and TLPD-FPC, cellular uptake of TLPD-FPM was significantly greater than that of TLPD-FPC in EGFR-overexpressing SMMC-7721 cells. The luciferase gene silencing efficiency of TLPD-FPM was approximately three-fold high than that of TLPD-FPC. Conclusion: Different conjugation linkers whereby antibodies are conjugated with LPD can affect the physicochemical properties of LPD and antibody conjugation efficiency, thus directly affecting the gene silencing effect of TLPD. Immunoliposomes prepared by DSPE-PEG-MAL conjugation with anti-EGFR Fab’ are more effective than TLPD containing DSPE-PEG-COOH in targeting hepatocellular carcinoma cells for siRNA delivery. Keywords: liposome-polycation-DNA, anti-EGFR Fab’, immunoliposomes, small interfering RNA delivery, conjugation technology, hepatocellular carcinoma |
| format |
article |
| author |
Deng L Zhang Y Ma L Jing X Ke X Lian J Zhao Q Yan B Zhang J Yao J Chen J |
| author_facet |
Deng L Zhang Y Ma L Jing X Ke X Lian J Zhao Q Yan B Zhang J Yao J Chen J |
| author_sort |
Deng L |
| title |
Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells |
| title_short |
Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells |
| title_full |
Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells |
| title_fullStr |
Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells |
| title_full_unstemmed |
Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells |
| title_sort |
comparison of anti-egfr-fab’ conjugated immunoliposomes modified with two different conjugation linkers for sirna delivery in smmc-7721 cells |
| publisher |
Dove Medical Press |
| publishDate |
2013 |
| url |
https://doaj.org/article/b6e5d2172e6d4695a10c50378a6df3fa |
| work_keys_str_mv |
AT dengl comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT zhangy comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT mal comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT jingx comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT kex comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT lianj comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT zhaoq comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT yanb comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT zhangj comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT yaoj comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells AT chenj comparisonofantiegfrfabrsquoconjugatedimmunoliposomesmodifiedwithtwodifferentconjugationlinkersforsirnadeliveryinsmmc7721cells |
| _version_ |
1718399302789758976 |