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Anticancer Agents Med Chem. 2019 Jul 2. doi: 10.2174/1871520619666190702145609. [Epub ahead of print]

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

Author information

1
Sir CV Raman-KS Krishnan International Research Center, Kalasalingam University, Krishnankoil-626126. India.
2
Department of Research and Development, Saraswathi Institute of Medical Sciences, NH-24, Anwarpur, Pilkhuwa, Hapur-245304, Uttar Pradesh. India.
3
Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy-502294, Telangana. India.
4
Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru-560054, Karnataka. India.
5
Department of Pharmacy, Birla Institute of Technology and Science, Pilani-333031. India.
6
Department of Hydrobiology, Faculty of Biology, University of Warsaw at Biology & Chemistry Research Center, 02-189-Warsaw. Poland.

Abstract

PURPOSE:

Site specific and toxic free drug delivery is an interesting area of research. Nano-engineered drug delivery systems possess remarkable potential for effective treatment of various types of cancers.

METHODS:

In this view, a novel Folic Acid (FA) conjugated keratin nanoparticles (NPs) were assembled with encapsulation and delivery of Rutin (Rt) in to breast cancer cells through over expressed folate receptor. The biocompatible Rt encapsulated FA conjugated keratin NPs (FA@Ker NPs) was successfully formulated by modified precipitation technique. Their morphological shape and size, size distribution, stability, and physical nature was characterized and confirmed. The drug (Rt) encapsulation efficiency, loading capacity and release kinetics were also studied.

RESULTS:

The observed results of molecular docking and density functionality theory of active drug (Rt) showed strong interaction and non-covalent binding of folate receptor and facilitation of endocytosis in to breast cancer cells. Further, in vitro cytotoxic effect of FA@Ker NPs was screened against MCF-7 cancer cells, at 55.2 µg/mL of NPs and found to display 50% of cell death at 24h. The NPs enhances uptake of Rt in MCF-7 cells, apoptotic effect of condensed nuclei and distorted membrane bodies was observed. Moreover, NPs enter in to mitochondria of MCF-7 cells and significantly increases the level of ROS which leads to cell death.

CONCLUSION:

The developed FA@Ker NPs might be promising way for enhanced anti-cancer activity without disturbed normal healthy cells.

KEYWORDS:

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

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