Design, In Silico Modelling, and Functionality Theory of Novel Folate Receptor Targeted Rutin Encapsulated Folic Acid Conjugated Keratin Nanoparticles for Effective Cancer Treatment

Author(s):

Selvaraj Kunjiappan, Theivendren Panneerselvam*, Saravanan Govindaraj, Pavadai Parasuraman, Suraj Baskararaj, Murugesan Sankaranarayanan, Sankarganesh Arunachalam, Ewa Babkiewicz, Aarthi Jeyakumar and Muthulakshmi Lakshmanan   Pages 1966 - 1982 ( 17 )

Abstract:

<P>Objective: Site-specific and toxic-free drug delivery, is an interesting area of research. Nanoengineered drug delivery systems possess a remarkable potential for effective treatment of various types of cancers. </P><P> Methods: In this study, novel Folic Acid (FA) conjugated keratin nanoparticles (NPs) were assembled with encapsulation and delivery of Rutin (Rt) into breast cancer cells through the overexpressed folate receptor. The biocompatible, Rt encapsulated FA conjugated keratin NPs (FA@Ker NPs) were successfully formulated by a modified precipitation technique. Their morphological shape and size, size distribution, stability, and physical nature were characterized and confirmed. The drug (Rt) encapsulation efficiency, loading capacity and release kinetics were also studied. </P><P> Results: The observed results of molecular docking and density functionality theory of active drug (Rt) showed a strong interaction and non-covalent binding of the folate receptor and facilitation of endocytosis in breast cancer cells. Further, in vitro cytotoxic effect of FA@Ker NPs was screened against MCF-7 cancer cells, at 55.2 &#181;g/mL of NPs and found to display 50% of cell death at 24h. Moreover, the NPs enhanced the uptake of Rt in MCF-7 cells, and the apoptotic effect of condensed nuclei and distorted membrane bodies was observed. Also, NPs entered into the mitochondria of MCF-7 cells and significantly increased the level of ROS which led to cell death. </P><P> Conclusion: The developed FA@Ker NPs might be a promising way to enhance anti-cancer activity without disturbing normal healthy cells.</P>

Keywords:

Rutin, folate receptor, drug delivery, breast cancer, keratin nanoparticles, MCF-7.

Affiliation:

Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126, Department of Research and Development, Saraswathi Institute of Medical Sciences, NH-24, Anwarpur, Pilkhuwa, Hapur-245304, Uttar Pradesh, Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy-502294, Telangana, Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bengaluru-560054, Karnataka, Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126, Department of Pharmacy, Birla Institute of Technology and Science, Pilani-333031, Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126, Department of Hydrobiology, Faculty of Biology, University of Warsaw at Biology & Chemistry Research Center, 02-189-Warsaw, Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126, Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126

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