Nano particle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance

JOURNAL OF CONTROLLED RELEASE

卷:141

Article

Khdair, Ayman^2,3  Chen, Di⁴  Patil, Yogesh²  Ma, Linan⁵  Dou, Q. Ping⁴  Shekhar, Malathy P. V.^6,7  Panyam, Jayanth^1,5 

[1] Univ Minnesota, Dept Pharmaceut, Coll Pharm, Minneapolis, MN 55455 USA

[2] Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Detroit, MI 48201 USA

[3] Appl Sci Univ, Dept Pharmaceut Sci & Pharmaceut, Amman 11931, Jordan

[4] Karmanos Canc Inst, Populat Studies Program, Detroit, MI 48201 USA

[5] Mason Canc Ctr, Minneapolis, MN 55455 USA

[6] Karmanos Canc Inst, Breast Canc Program, Detroit, MI 48201 USA

[7] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA

关键词: Chemotherapy;    Nanoparticles;    Photosensitizer;    Drug efflux;    Drug resistance;    Reactive oxygen species;   

DOI  :  10.1016/j.jconrel.2009.09.004

来源: Elsevier

【 摘 要 】

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 (TM) (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. (C) 2009 Elsevier B.V. All rights reserved.

【 授权许可】

Free