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Issue 47, 2017, Issue in Progress
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Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

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Abstract

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-co-DMAAm)] 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 pH-responsive micelles against human cervical cancer HeLa cells was significantly greater at 42 °C than at 37 °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.

Graphical abstract: Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

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Publication details

The article was received on 28 Mar 2017, accepted on 31 May 2017 and first published on 06 Jun 2017


Article type: Paper
DOI: 10.1039/C7RA03579A
Citation: RSC Adv., 2017,7, 29540-29549
  • Open access: Creative Commons BY license
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    Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery

    Y. Hiruta, Y. Kanda, N. Katsuyama and H. Kanazawa, RSC Adv., 2017, 7, 29540
    DOI: 10.1039/C7RA03579A

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