Journal
RSC ADVANCES
Volume 7, Issue 47, Pages 29540-29549Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7ra03579a
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [15K18846]
- Research Foundation for Pharmaceutical Sciences
- Grants-in-Aid for Scientific Research [15K18846] Funding Source: KAKEN
Ask authors/readers for more resources
We report a polymeric micelle drug delivery system, which enables selective intracellular uptake with external thermal stimulation, and effective release of a drug at internal acidic endosomal pH. We developed a dual temperature-and pH-responsive polymeric micelle composed of a temperature-responsive corona segment with poly(N-isopropylacrylamide-co-dimethylacrylamide) [P(NIPAAm-coDMAAm)] and a pH-responsive core segment with poly[2-(diisopropylamino) ethyl methacrylate] (PDPA). A dual temperature-and pH-responsive amphiphilic diblock copolymer was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The dithiobenzoate end-group was removed with radical-induced ester exchange. This copolymer formed nano-sized micelles in aqueous solution, and encapsulated anti-cancer agent, doxorubicin (DOX). The resultant micelles exhibited a temperature-dependent phase transition at a temperature slightly higher than body temperature, and intracellular uptake of encapsulated DOX was accelerated above the phase transition temperature. A transition from neutral to positive charge, leading to micelle disassembly, accelerated the release of Nile red as a model drug. The cytotoxicity of doxorubicin (DOX)-loaded dual temperature-and pHresponsive micelles against human cervical cancer HeLa cells was significantly greater at 42 degrees C than at 37 degrees C, while no significant temperature-dependent cytotoxicity was observed with DOX-loaded micelles that were only temperature-responsive. This proof-of-concept synergistic two-step delivery system with enhanced intracellular uptake upon external thermal stimulation and rapid release of DOX at internal acidic endosomal pH was effective against tumor cells in vitro.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available