Abstract |
We first synthesized indomethacin (IND)-grafted dextran copolymer by acetal or ester linkage, which self-assembled with doxorubicin (DOX) into prodrug micelles (IDAC/DOX or IDES/DOX) with the size of ∼200 nm. In vitro drug release test verified IDAC/DOX could trigger more DOX and IND release by the hydrolysis of acetal than that of ester linkage. A series cells experiments demonstrated pH-sensitive IDAC/DOX could greatly improve cellular uptake and intracellular drug accumulation, thus enhancing DOX toxicity in drug-resistant tumor cells. IDAC/DOX was capable of reversing tumor multidrug resistance (MDR) through reducing multidrug resistance-associated protein 1 ( MRP1) level (0.23-fold vs control group) and regulating bcl-2/bax pathway, eventually induced more apoptosis in MCF-7/ADR cells. These nanoparticles possessed long-term blood-circulation and high tumor accumulation, thereby reducing side effect and increasing bioavailability. Anti- tumor evaluation showed that IDAC/DOX possessed the highest tumor growth inhibition (TGI, 92.5 %), which might provide a promising way to overcome malignant tumor resistance.
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Authors | Xiaoli Zeng, Xu Cheng, Yan Zheng, Guoqing Yan, Xin Wang, Jun Wang, Rupei Tang |
Journal | Carbohydrate polymers
(Carbohydr Polym)
Vol. 237
Pg. 116139
(Jun 01 2020)
ISSN: 1879-1344 [Electronic] England |
PMID | 32241443
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier Ltd. All rights reserved. |
Chemical References |
- Dextrans
- Drug Carriers
- Micelles
- Doxorubicin
- Indomethacin
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Topics |
- Adenocarcinoma
(drug therapy)
- Animals
- Breast Neoplasms
(drug therapy)
- Dextrans
(chemistry)
- Doxorubicin
(administration & dosage)
- Drug Carriers
(therapeutic use)
- Drug Resistance, Multiple
(drug effects)
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Humans
- Indomethacin
(chemistry)
- MCF-7 Cells
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Micelles
- Nanoparticles
(therapeutic use)
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