Dataset Information
PH and redox dual-responsive copolymer micelles with surface charge reversal for co-delivery of all-trans-retinoic acid and paclitaxel for cancer combination chemotherapy.
Ontology highlight
ABSTRACT: Background
Co-delivery all-trans-retinoic acid (ATRA) and paclitaxel (PTX) is an effective strategy for cancer therapy. However, in many previous reported ATRA conjugated co-delivery systems, the ATRA was released slower than PTX, and the total drug release of ATRA far lower than that of PTX.Purpose
We designed and prepared a pH and redox dual responsive drug delivery system (DA-ss-NPs) co-delivery ATRA and PTX for cancer therapy. The surface charge of DA-ss-NPs could change from negative to positive under tumor slightly acidic microenvironment, and both drugs could be quickly released from DA-ss-NPs under intracellular high concentration of glutathione (GSH).Methods
The DA-ss-NPs were constructed by encapsulating PTX into the hydrophobic core of the polymer micelles, in which the polymer was synthesized by conjugating ATRA and 2,3-Dimethylmalefic anhydride (DMA) on side chains of Cystamine dihydrochloride (Cys) modified PEG-b-PAsp (named DA-ss-NPs). The surface charge of DA-ss-NPs under different pH conditions were detected. And the drug release was also measured under different concentration of GSH. The therapeutic effect of DA-ss-NPs were investigated in Human lung cancer A549 cells and A549 tumor-bearing mice.Results
The zeta potential of DA-ss-NPs was -16.3 mV at pH 7.4, and which changed to 16 mV at pH 6.5. Cell uptake experiment showed that more DA-ss-NPs were internalized by A549 cells at pH 6.5 than that at pH 7.4. In addition, in presence of 10 mM GSH at pH 7.4, about 75%-85% ATRA was released from DA-ss-NPs within 48 h; but less than 20% ATRA was released without GSH. In vivo antitumor efficiency showed that the DA-ss-NPs could affectively inhibite the tumor in compared with control groups.Conclusion
The charge-reversal and GSH-responsive DA-ss-NPs provide an excellent platform for potential tumor therapy.
SUBMITTER: Zhang Y
PROVIDER: S-EPMC6199233 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
pH and redox dual-responsive copolymer micelles with surface charge reversal for co-delivery of all-<i>trans</i>-retinoic acid and paclitaxel for cancer combination chemotherapy.
International journal of nanomedicine 20181016
<h4>Background</h4>Co-delivery all-trans-retinoic acid (ATRA) and paclitaxel (PTX) is an effective strategy for cancer therapy. However, in many previous reported ATRA conjugated co-delivery systems, the ATRA was released slower than PTX, and the total drug release of ATRA far lower than that of PTX.<h4>Purpose</h4>We designed and prepared a pH and redox dual responsive drug delivery system (DA-ss-NPs) co-delivery ATRA and PTX for cancer therapy. The surface charge of DA-ss-NPs could change from ...[more]