pH-Sensitive Dextran-Based Micelles from Copper-Free Click Reaction for Antitumor Drug Delivery
There remains a need to develop new strategies to fabricate dextran-based biocompatible drug delivery systems for safe and effective chemotherapy. Herein, a copper-free azide-propiolate ester click reaction was introduced for dextran modification to fabricate a pH-sensitive dextran-based drug delive...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 37(2021), 44 vom: 09. Nov., Seite 12990-12999 |
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| Weitere Verfasser: | , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2021
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Antineoplastic Agents Dextrans Drug Carriers Micelles Doxorubicin 80168379AG |
| Zusammenfassung: | There remains a need to develop new strategies to fabricate dextran-based biocompatible drug delivery systems for safe and effective chemotherapy. Herein, a copper-free azide-propiolate ester click reaction was introduced for dextran modification to fabricate a pH-sensitive dextran-based drug delivery system. A pH-sensitive dextran-based micelle system, self-assembled from amphiphilic dextran-graft-poly(2-(diisopropylamino)ethyl methacrylate-co-2-(2',3',5'-triiodobenzoyl)ethyl methacrylate) or dextran-g-P(DPA-co-TIBMA), is reported for effective chemotherapy. The amphiphilic dextran-g-P(DPA-co-TIBMA) was prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization and copper-free azide-propiolate ester click reaction. Doxorubicin (DOX)-loaded dextran-g-P(DPA-co-TIBMA) micelles were prepared through self-assembly of DOX and dextran-g-P(DPA-co-TIBMA) in aqueous solution, and had a mean diameter of 154 nm and a drug loading content of 9.7 wt %. The release of DOX from DOX-loaded dextran-g-P(PDPA-co-TIBMA) micelles was slow at pH 7.4, but was greatly accelerated under acidic conditions (pH 6 and 5). Confocal laser scanning microscopy and flow cytometry experiments showed that the dextran-g-P(DPA-co-TIBMA) micelles could effectively deliver and release DOX in human breast cancer cell line (MCF-7 cells). MTT assay showed that dextran-g-P(DPA-co-TIBMA) exhibited excellent biocompatibility while DOX-loaded dextran-g-P(DPA-co-TIBMA) micelles have good antitumor efficacy in vitro. The in vivo therapeutic studies indicated that the DOX-loaded dextran-g-P(PDPA-co-TIBMA) micelles could effectively reduce the growth of tumor with little body weight reduction |
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| Beschreibung: | Date Completed 27.01.2022 Date Revised 27.01.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.1c02049 |