Journal
LANGMUIR
Volume 37, Issue 44, Pages 12990-12999Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.1c02049
Keywords
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Funding
- Singapore Millennium Foundation [1123004048, R279-000-428-592]
- Natural Science Foundation of China [21404115]
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials [XMHT20190204007]
- Shenzhen High-level Hospital Construction Fund
- Shenzhen Key Medical Discipline Construction Fund [SZXK023]
- Shenzhen San-Ming Project of Medicine [SZSM201612092]
- Shenzhen Science and Technology Program [JCYJ20210324105806016]
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This study introduces a novel dextran-based drug delivery system that exhibits pH sensitivity during cancer chemotherapy. Experimental results show that the system has good biocompatibility and anti-tumor effects in vitro, while in vivo studies demonstrate its effectiveness in inhibiting tumor growth with minimal weight loss.
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 dextranbased drug delivery system. A pH-sensitive dextran-based micelle system, self-assembled from amphiphilic dextran-graf t-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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