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Dual-Responsive Polymer Micelles for Target-Cell-SpecificAnticancer Drug Delivery.
- Source :
-
Chemistry of Materials . Aug2014, Vol. 26 Issue 15, p4405-4418. 14p. - Publication Year :
- 2014
-
Abstract
- Efficientdelivery of therapeutic agents with nanocarriers intothe nucleus to achieve high therapeutic efficiency is still a majorchallenge for cancer therapy due to mucosal barriers, nonspecificuptake, and intracellular drug resistance. In this study, we developa dual-responsive polymer micelle system with sheddable polyethylenimine(PEI) shells for actively targeted drug delivery. This system exhibitsan ultrasensitive negative-to-positive charge reversal in responseto the extracellular pH value, resulting in greatly enhanced uptakeby cancer cells via electrostatic interaction. Moreover, the activetargeting ability can further promote the selective uptake of thenanocarriers in the cancer cell. Once the micelles escape from thelysosomes, the disulfide linkages can be cleaved by GSH in the cytoplasm,and in turn the hydrophilic PEI shell is deshielded, leading to therapid release of the encapsulated agent into the nuclei. The antitumoractivity in 4T1 tumor-bearing mice reveals that this novel systempossesses a long blood circulation due to the originally negativelycharged surface and can significantly promote the cell internalizationand intracellular drug release, thus leading to a high therapeuticefficacy against resistant tumors and fewer side effects to normaltissues. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08974756
- Volume :
- 26
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Chemistry of Materials
- Publication Type :
- Academic Journal
- Accession number :
- 97441620
- Full Text :
- https://doi.org/10.1021/cm5012718