Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery
© 2016 Acta Materialia Inc.Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-func...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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Elsevier BV
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/52894 |
| _version_ | 1848759037698506752 |
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| author | Lin, Qun Yang, Y. Hu, Q. Guo, Z. Liu, T. Xu, J. Wu, J. Kirk, T. Ma, D. Xue, W. |
| author_facet | Lin, Qun Yang, Y. Hu, Q. Guo, Z. Liu, T. Xu, J. Wu, J. Kirk, T. Ma, D. Xue, W. |
| author_sort | Lin, Qun |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2016 Acta Materialia Inc.Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with a-cyclodextrin (a-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by a-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on a-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate for long-term gene therapy. Statement of Significance To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering. |
| first_indexed | 2025-11-14T09:53:31Z |
| format | Journal Article |
| id | curtin-20.500.11937-52894 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:53:31Z |
| publishDate | 2017 |
| publisher | Elsevier BV |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-528942017-09-13T15:39:43Z Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery Lin, Qun Yang, Y. Hu, Q. Guo, Z. Liu, T. Xu, J. Wu, J. Kirk, T. Ma, D. Xue, W. © 2016 Acta Materialia Inc.Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with a-cyclodextrin (a-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by a-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on a-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate for long-term gene therapy. Statement of Significance To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering. 2017 Journal Article http://hdl.handle.net/20.500.11937/52894 10.1016/j.actbio.2016.11.062 Elsevier BV restricted |
| spellingShingle | Lin, Qun Yang, Y. Hu, Q. Guo, Z. Liu, T. Xu, J. Wu, J. Kirk, T. Ma, D. Xue, W. Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery |
| title | Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery |
| title_full | Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery |
| title_fullStr | Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery |
| title_full_unstemmed | Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery |
| title_short | Injectable supramolecular hydrogel formed from a-cyclodextrin and PEGylated arginine-functionalized poly(L-lysine) dendron for sustained MMP-9 shRNA plasmid delivery |
| title_sort | injectable supramolecular hydrogel formed from a-cyclodextrin and pegylated arginine-functionalized poly(l-lysine) dendron for sustained mmp-9 shrna plasmid delivery |
| url | http://hdl.handle.net/20.500.11937/52894 |