An in-Silico approach to evaluate the binding efficacy and stability profile of MWCNT entangled rutin for breast cancer treatment

Document Type : Research Paper

Authors

1 Department of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru-560054, Karnataka, India

2 Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil-626126, Tamilnadu, India

3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru-560054, Karnataka, India

Abstract

Objective(s): Cancer is one of the most devastating diseases and ranks second in a total number of deaths caused globally. In recent years there is a steady increase in breast cancer (BC) incidence due to several etiological factors. Due to indiscriminate drug delivery and the lack of target specificity, current cancer therapies can cause life-threatening side effects. The present research emphasises targeting the rutin-loaded onto carbon nanotubes (CNTs) for breast cancer treatment. Further, rutin-loaded multi-walled carbon nanotube (MWCNT) and conjugated with folic acid is the focus of our research against breast cancer. 
Materials and Methods: Intermolecular interaction studies between rutin (PubChem CID 5280805) and the target protein folate receptor (PDB ID 4LRH) via Autodock Vina programme and PyRx tool and molecular dynamics simulation studies were performed.  
Results: The docking score was found to be -8.7 Kcal mol-1. In comparison, that of the standard chemotherapeutic drug 5-Fluorouracil was -5.9 Kcal mol-1. Molecular dynamic studies were performed via Desmond for 100ns. The root-mean-square deviation (RMSD) value of the ligand remained stable, root-mean-square fluctuation (RMSF) values have been observed to be stable throughout the simulation time. 
Conclusion: Based on these promising results, rutin-loaded CNTs can be further evaluated for their efficacy against breast cancer preclinically.

Keywords

References

1.    McGuire S. World cancer report 2014. Geneva, Switzerland: World Health Organization, international agency for research on cancer, WHO Press, 2015. Adv Nutr. 2016;7(2):418-419.
2.    Harrop JP, Dean JA, Paskett ED. Cancer survivorship research: a review of the literature and summary of current NCI-designated cancer center projects. Cancer Epidemiol Biomarkers Prev. 2011; 20(10):2042-2047.
3.    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. 2021; 71(3):209-249.
4.    Alkabban FM, Ferguson T. Cancer, breast. 2018.
5.    Duan J, Bao C, Xie Y, Guo H, Liu Y, Li J, Liu R, Li P, Bai J, Yan Y. Targeted core-shell nanoparticles for precise CTCF gene insert in treatment of metastatic breast cancer. Bioact Mat. 2022; 11:1-14.
6.    Weigelt B, Horlings H, Kreike B, Hayes M, Hauptmann M, Wessels L, De Jong D, Van de Vijver M, Veer LVt, Peterse J. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol: J Pathol Soc Great Britain Ireland 2008; 216(2):141-150.
7.    Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current challenges in cancer treatment. Clin Ther. 2016; 38(7):1551-1566.
8.    Pucci C, Martinelli C, Ciofani G. Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedicalscience 2019; 13.
9.    Rothenberg ML, Carbone DP, Johnson DH. Improving the evaluation of new cancer treatments: challenges and opportunities. Nat Rev Cancer 2003; 3(4):303-309.
10.    Norton N, Youssef B, Hillman DW, Nassar A, Geiger XJ, Necela BM, Liu H, Ruddy KJ, Polley M-YC, Ingle JN. Folate receptor alpha expression associates with improved disease-free survival in triple negative breast cancer patients. NPJ Breast Cancer 2020; 6(1):1-9.
11.    O’Shannessy DJ, Somers EB, Maltzman J, Smale R, Fu Y-S. Folate receptor alpha (FRA) expression in breast cancer: identification of a new molecular subtype and association with triple negative disease. Springerplus 2012; 1(1):1-9.
12.    Zhang Y, Li M, Gao X, Chen Y, Liu T. Nanotechnology in cancer diagnosis: progress, challenges and opportunities. J Hematol Oncol. 2019; 12(1):1-13.
13.    Awasthi R, Roseblade A, Hansbro PM, Rathbone MJ, Dua K, Bebawy M. Nanoparticles in cancer treatment: opportunities and obstacles. Curr Drug Targets 2018; 19(14):1696-1709.
14.    Gmeiner WH, Ghosh S. Nanotechnology for cancer treatment. Nanotechnol Rev. 2014; 3(2):111-122.
15.    Kaur J, Gill GS, Jeet K. Applications of carbon nanotubes in drug delivery: A comprehensive review. Characterization and biology of nanomaterials for drug delivery 2019; 113-135.
16.    Ahmed A, Sarwar S, Hu Y, Munir MU, Nisar MF, Ikram F, Asif A, Rahman SU, Chaudhry AA, Rehman IU. Surface-modified polymeric nanoparticles for drug delivery to cancer cells. Expert Opin Drug Deliv. 2021; 18(1):1-24.
17.    Mahajan S, Patharkar A, Kuche K, Maheshwari R, Deb PK, Kalia K, Tekade RK. Functionalized carbon nanotubes as emerging delivery system for the treatment of cancer. Int J Pharm. 2018; 548(1):540-558.
18.    Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, Prakash O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Front Pharmacol. 2020; 10:1614.
19.    Khatoon E, Banik K, Harsha C, Sailo BL, Thakur KK, Khwairakpam AD, Vikkurthi R, Devi TB, Gupta SC, Kunnumakkara AB. Phytochemicals in cancer cell chemosensitization: Current knowledge and future perspectives. In: Semin Cancer Biol. 2022; Elsevier: 306-339.
20.    Vijayalakshmi S, Rajasekar A, Veeraraghavan VP, Ghidan AY, Al Antary TM, Karthikkumar V, Damodaran LPM, Vinayagam R, David E. The pro-apoptotic and cytotoxic efficacy of polydatin encapsulated poly (lactic-co-glycolic acid)(PLGA) nanoparticles. Process Biochem. 2021; 111:210-218.
21.    Imani A, Maleki N, Bohlouli S, Kouhsoltani M, Sharifi S, Maleki Dizaj S. Molecular mechanisms of anticancer effect of rutin. Phytother Res. 2021; 35(5):2500-2513.
22.    Alsaif NA, Wani TA, Bakheit AH, Zargar S. Multi-spectroscopic investigation, molecular docking and molecular dynamic simulation of competitive interactions between flavonoids (quercetin and rutin) and sorafenib for binding to human serum albumin. Int J Biol Macromol. 2020; 165:2451-2461.
23.    Kalimuthu AK, Panneerselvam T, Pavadai P, Pandian SRK, Sundar K, Murugesan S, Ammunje DN, Kumar S, Arunachalam S, Kunjiappan S. Pharmacoinformatics-based investigation of bioactive compounds of Rasam (South Indian recipe) against human cancer. Sci Rep. 2021; 11(1):1-19.
24.    Klepeis JL, Lindorff-Larsen K, Dror RO, Shaw DE. Long-timescale molecular dynamics simulations of protein structure and function. Curr Opin Struct Biol. 2009; 19(2):120-127.
Nanomedicine Journal
Volume 10, Issue 3
July 2023
Pages 210-215

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