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

Abstract

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. 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. 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 µg/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. Conclusion: The developed FA@Ker NPs might be a promising way to enhance anti-cancer activity without disturbing normal healthy cells.

Graphene Oxide Nanosheets Interact and Interfere with SARS‐CoV‐2 Surface Proteins and Cell Receptors to Inhibit Infectivity

“…[4] Based on the data generated by such in silico analyses, nanotechnology-based therapeutic approaches could be improved. [51][52][53] Among 2D materials, GO is the most studied one using such computational models to depict interactions with various biological moieties, mainly proteins. [54][55][56][57][58][59][60][61] For example, Baweja et al reported that GO and reduced GO (rGO) were able to inhibit the α-helix to β-sheet transition of amyloid beta (Aβ) peptide, which has been implicated in the pathogenesis of Alzheimer's disease.…”

Anticancer drug discovery from Iranian Chrysanthemum cultivars through system pharmacology exploration and experimental validation

“…Previous research showed that rutin encapsulated in folic acid conjugated keratin nanoparticles significantly increased the level of ROS, which led to cell death in MCF-7 breast cancer cell lines while exhibiting less toxicity in normal cells. Furthermore, the nanoparticles enhanced the uptake of rutin in MCF-7 cells 36 . Quercetin easily passes through the colon barrier as a rutin metabolite and leads to biological effects.…”

Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

“…Rutin encapsulated in folic acid conjugated keratin NPs promotes cell death in MCF-7 breast cancer cells while exhibiting less toxicity in healthy cells [ 230 ] ( Table 2 ). Additionally, the actively targeted nanoformulation decreases tumor cell migration, elevates rutin uptake in cancer cells, and boosts apoptosis through ROS production and mitochondrial potential loss.…”

“…Additionally, the actively targeted nanoformulation decreases tumor cell migration, elevates rutin uptake in cancer cells, and boosts apoptosis through ROS production and mitochondrial potential loss. An in vitro study indicated that the nanoformulation selectively targets breast cancer cells [ 230 ]. However, in vivo studies are needed to confirm the active targeted delivery of folic acid conjugated keratin NPs.…”