Doxorubicin loaded pH-sensitive micelle: Antitumoral efficacy against ovarian A2780/DOXR tumor

Dongin Kim, Eun Seong Lee, Kyeongsoon Park, Ick Chan Kwon, You Han Bae

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)


Purpose. To evaluate pH-sensitive mixed micelles for multidrug resistant (MDR) ovarian tumor targeting and optical imaging of solid tumors. Method. Doxorubicin (DOX) encapsulated pH-sensitive mixed micelles composed of poly(l-histidine)(MW 5K)-b-PEG(MW 2K) and poly(l-lactic acid)(3K)-b-PEG (2K)-folate (PHSM-f) were prepared. Folate receptor-mediated endocytosis, drug uptake, endosomal disruption and cell viability were investigated at the cellular level. For in vivo tumor growth inhibition tests, multidrug resistant ovarian A2780/DOXR xenografted nude mice were used. Optical imaging was performed by using a Cy5.5 fluorescence dye-labeled mixed micelle system. Cy5.5 fluorescence intensity at the tumor site was measured in KB epidermoid xenografted nude mice. Results. In vitro cell viability and drug distribution in the cytoplasm demonstrated the significantly superior efficacy of PHSM-f to free DOX and a control sample of DOX loaded pH-insensitive micelle composed of poly(l-lactic acid)(3K)-b-PEG(2K)/poly(l-lactic acid)(3K)-b-PEG(2K)-folate (80/20 wt/wt%) (PHIM-f). The mechanisms of these results were proved by folate receptor mediated endocytosis of micelle and endosomal disruption function by it. In addition, the optical imaging demonstrated the future application of the diagnositic area. PHSM-f inhibited the growth of multidrug resistant ovarian tumors efficiently in mice, with minimum weight loss. Conclusions. The pH-sensitive mixed micelle system demonstrates effective antitumor efficacy against the multidrug resistant ovarian tumor A2780/DOXR.

Original languageEnglish
Pages (from-to)2074-2082
Number of pages9
JournalPharmaceutical research
Issue number9
Publication statusPublished - 2008 Sept

Bibliographical note

Funding Information:
This work was partially supported by NIH CA 101850. Drs. Zhonggao Gao, Kyung Taek Oh, and Han Chang Kang are acknowledged for their help with various experiments.


  • Folic acid
  • Micelle
  • Multidrug resistance
  • Ovarian cancer
  • Poly(L-histidine)

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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