TY - JOUR
T1 - Strategic design of potential siRNA molecules for in vitro Evaluation in ABCG2 resistant Breast cancer and in vivo toxicity Determination
AU - Gatta, Aditya Kiran
AU - Philip, Nancy V.
AU - Raghu, Chandrashekhar H.
AU - Udupa, N.
AU - Reddy, Meka Sreenivasa
AU - Mutalik, Srinivas
AU - Josyula, Venkata Rao
N1 - Funding Information:
The authors acknowledge Nano Mission Council of the Department of Science and Technology, the Govt. of India, New Delhi (SR/NM/NS-1090/2012 (G)) and authorities from the Manipal Academy of Higher Education (MAHE). We also thank Daphne Crasta for the support in the study.
Publisher Copyright:
© RJPT All right reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Better understanding of breast cancer and drug resistance is possible today due to significant advancements in the field of cell and molecular biology. In this study, we provide a therapeutic approach (Ch-PLGA-siRNA NP) to downregulate the ABCG2 pump, highly expressed in drug resistant breast cancer. Methods: We designed an efficient siRNA, evaluated its binding and off targeting properties. Further, formulated and assessed for the in vitro potency and in vivo toxicity. Results: Three potential siRNA molecules, satisfying the important criteria with specificity towards ABCG2, were designed and validated. Further the siRNA molecules were delivered to the drug resistant breast cancer cells using the nanoparticles and observed for the levels of reduction in the expression of ABCG2. We then tested the formulation loaded with siRNA for acute toxicity in Swiss albino mice and found to be non toxic in nature. Conclusion: This study proved that the designed siRNA molecules as very potent moieties against ABCG2 resistant breast cancer with non toxic profile in vivo.
AB - Better understanding of breast cancer and drug resistance is possible today due to significant advancements in the field of cell and molecular biology. In this study, we provide a therapeutic approach (Ch-PLGA-siRNA NP) to downregulate the ABCG2 pump, highly expressed in drug resistant breast cancer. Methods: We designed an efficient siRNA, evaluated its binding and off targeting properties. Further, formulated and assessed for the in vitro potency and in vivo toxicity. Results: Three potential siRNA molecules, satisfying the important criteria with specificity towards ABCG2, were designed and validated. Further the siRNA molecules were delivered to the drug resistant breast cancer cells using the nanoparticles and observed for the levels of reduction in the expression of ABCG2. We then tested the formulation loaded with siRNA for acute toxicity in Swiss albino mice and found to be non toxic in nature. Conclusion: This study proved that the designed siRNA molecules as very potent moieties against ABCG2 resistant breast cancer with non toxic profile in vivo.
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U2 - 10.5958/0974-360X.2021.00011.1
DO - 10.5958/0974-360X.2021.00011.1
M3 - Article
AN - SCOPUS:85135193454
SN - 0974-3618
VL - 14
SP - 55
EP - 61
JO - Research Journal of Pharmacy and Technology
JF - Research Journal of Pharmacy and Technology
IS - 1
ER -
