The accumulation of dual pH and temperature responsive micelles in tumors

Yi Chun Chen, Li Chi Liao, Pei Lin Lu, Chun Liang Lo, Hsieh Chih Tsai, Chiung Yin Huang, Kuo Chen Wei, Tzu Chen Yen, Ging Ho Hsiue*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

73 Scopus citations

Abstract

An optimized, biodegradable, dual temperature- and pH-responsive micelle system conjugated with functional group Cy5.5 was prepared in order to enhance tumor accumulation The Dynamic light scattering (DLS) measurements showed that these diblock copolymers form micelle in PBS buffer with a size of around 50 nm by heating of an aqueous polymer solution from below to above the cloud point (CP) Anticancer drug, doxorubicin was incorporated into the inner core of micelle by hot shock protocol The size and stability of the micelle were controlled by the copolymer composition and is fine tuned to extracellular pH of tumor The mechanism then caused pH change and at body temperature which induce doxorubicin release from micelles and have strong effects on the viability of HeLa, ZR-75-1, MCF-7 and H661 cancer cells Our in vivo results revealed a clear distribution of Doxorubicin-loaded mixed micelle (Dox-micelle) and efficiency targeting tumor site with particles increasing size in the tumor interstitial space, and the particles could not diffuse throughout the tumor matrix In vivo tumor growth inhibition showed that Dox-micelle exhibited excellent antitumor activity and a high rate of anticancer drug in cancer cells by this strategy

Original languageEnglish
Pages (from-to)4576-4588
Number of pages13
JournalBiomaterials
Volume33
Issue number18
DOIs
StatePublished - 06 2012

Keywords

  • Doxorubicin
  • EPR effect
  • PH-responsive
  • Polymeric micelles
  • Temperature-responsive

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