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Abstract

Strategic Design of Dicer Substrate siRNA to Mitigate the Resistance Mediated by ABCC1 in Doxorubicin-resistant Breast Cancer

Author(s): A. K. GATTA, R. CHANDRASHEKHAR, N. UDUPA1, M. S. REDDY2, S. MUTALIK2 AND V. R. JOSYULA*
Cell and Molecular Biology lab, Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, 1Research Director (Health Sciences), 2Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Karnataka 576104, India

Correspondence Address:
2Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Karnataka 576104, India, E-mail: [email protected]

The current study involved designing of a small interfering ribonucleic acid-loaded folate functionalized chitosan-coated PLGA nanoparticles to evaluate tumor targeting potential in drug-resistant breast cancer cells. The synthesized conjugate was utilized to develop small interfering ribonucleic acid encapsulated nanoparticles. The developed siRNA nanoparticles were with a particle size of Ë?250 nm and could offer protection against serum nucleases. A significant uptake of the folic acid conjugated formulation was noticed, affirming that the nanoparticles selectively targeted the drug-resistant cancer cells. Through the polymerase chain reaction and Western blot, it was evident that ABCC1 expression was significantly reduced (Ë?95%). The efficiency of small interfering ribonucleic acid with doxorubicin could be evaluated by cytotoxicity assay and it was found that the ABCC1 targeted small interfering ribonucleic acid minimized the resistance of doxorubicin-resistant MCF- 7 cell line to doxorubicin. The main objective in developing this folate conjugated nanoformulation was to enhance the targetability to the cancer cells and to increase the sensitivity of drug-resistant tumors to doxorubicin.

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