Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance

Ayman Khdair, Chen Di Chen, Yogesh Patil, Linan Ma, Q. Ping Dou, Malathy P.V. Shekhar, Jayanth Panyam

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT™ (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalJournal of Controlled Release
Volume141
Issue number2
DOIs
StatePublished - Jan 25 2010

Bibliographical note

Funding Information:
The funding was from the Presidential Research Enhancement Program, Wayne State University . We thank Prof. Guangzhao Mao and Dr. Hitesh Handa for assistance with AFM characterization of nanoparticles.

Keywords

  • Chemotherapy
  • Drug efflux
  • Drug resistance
  • Nanoparticles
  • Photosensitizer
  • Reactive oxygen species

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