Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release
Injectable, covalently cross-linked hydrogels have been widely investigated in drug delivery systems due to their superior mechanical properties and long-term stability. Conventional covalently cross-linked hydrogels are formed by chemical reactions that may interfere with natural biochemical proces...
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MDPI AG
2020-04-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/12/4/884 |
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| author | Zhen Zhang Chaoliang He Xuesi Chen |
| author_facet | Zhen Zhang Chaoliang He Xuesi Chen |
| author_sort | Zhen Zhang |
| collection | DOAJ |
| description | Injectable, covalently cross-linked hydrogels have been widely investigated in drug delivery systems due to their superior mechanical properties and long-term stability. Conventional covalently cross-linked hydrogels are formed by chemical reactions that may interfere with natural biochemical processes. In this work, we developed an injectable polypeptide hydrogel via an inverse electron demand Diels-Alder reaction between norbornene modified poly(L-glutamic acid) (PLG-Norb) and tetrazine functionalized four-arm poly(ethylene glycol) (4aPEG-T) for localized release of cisplatin (CDDP). The rapid and bioorthogonal click reaction allowed for hydrogel formation within a few minutes after mixing the two polymer solutions in phosphate buffer saline (PBS). Dynamic mechanical analysis suggested that the storage modulus of the hydrogel could be readily tuned by changing the polymer concentration and the molar ratio of the two functional groups. The carboxyl groups of PLG-Norb were used to form polymer–metal complexation with CDDP, and the controlled release of the antitumor drug was achieved in PBS. The CDDP-loaded hydrogel displayed an antitumor effect against MCF-7 cells in vitro, through S phase cell cycle arrest. After subcutaneous injection in rats, the hydrogel was rapidly formed in situ and showed good stability in vivo. In an MCF-7-bearing nude mice model, the CDDP-loaded hydrogel exhibited an improved antitumor effect with reduced systemic toxicity. Overall, the injectable click polypeptide hydrogel shows considerable potential as a platform for localized and sustained delivery of antitumor drugs. |
| first_indexed | 2024-03-10T20:32:24Z |
| format | Article |
| id | doaj.art-df0575a6102f40589207521801ea35fd |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-10T20:32:24Z |
| publishDate | 2020-04-01 |
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| series | Polymers |
| spelling | doaj.art-df0575a6102f40589207521801ea35fd2023-11-19T21:18:55ZengMDPI AGPolymers2073-43602020-04-0112488410.3390/polym12040884Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin ReleaseZhen Zhang0Chaoliang He1Xuesi Chen2CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaCAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, ChinaInjectable, covalently cross-linked hydrogels have been widely investigated in drug delivery systems due to their superior mechanical properties and long-term stability. Conventional covalently cross-linked hydrogels are formed by chemical reactions that may interfere with natural biochemical processes. In this work, we developed an injectable polypeptide hydrogel via an inverse electron demand Diels-Alder reaction between norbornene modified poly(L-glutamic acid) (PLG-Norb) and tetrazine functionalized four-arm poly(ethylene glycol) (4aPEG-T) for localized release of cisplatin (CDDP). The rapid and bioorthogonal click reaction allowed for hydrogel formation within a few minutes after mixing the two polymer solutions in phosphate buffer saline (PBS). Dynamic mechanical analysis suggested that the storage modulus of the hydrogel could be readily tuned by changing the polymer concentration and the molar ratio of the two functional groups. The carboxyl groups of PLG-Norb were used to form polymer–metal complexation with CDDP, and the controlled release of the antitumor drug was achieved in PBS. The CDDP-loaded hydrogel displayed an antitumor effect against MCF-7 cells in vitro, through S phase cell cycle arrest. After subcutaneous injection in rats, the hydrogel was rapidly formed in situ and showed good stability in vivo. In an MCF-7-bearing nude mice model, the CDDP-loaded hydrogel exhibited an improved antitumor effect with reduced systemic toxicity. Overall, the injectable click polypeptide hydrogel shows considerable potential as a platform for localized and sustained delivery of antitumor drugs.https://www.mdpi.com/2073-4360/12/4/884injectable hydrogelpolypeptideclick chemistrylocal cisplatin delivery |
| spellingShingle | Zhen Zhang Chaoliang He Xuesi Chen Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release Polymers injectable hydrogel polypeptide click chemistry local cisplatin delivery |
| title | Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release |
| title_full | Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release |
| title_fullStr | Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release |
| title_full_unstemmed | Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release |
| title_short | Injectable Click Polypeptide Hydrogels via Tetrazine-Norbornene Chemistry for Localized Cisplatin Release |
| title_sort | injectable click polypeptide hydrogels via tetrazine norbornene chemistry for localized cisplatin release |
| topic | injectable hydrogel polypeptide click chemistry local cisplatin delivery |
| url | https://www.mdpi.com/2073-4360/12/4/884 |
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