A Minor Groove Binder with Significant Cytotoxicity on Human Lung Cancer Cells: The Potential of Hesperetin Functionalised Silver Nanoparticles

Overview

Journal J Fluoresc

Specialties Biophysics
Chemistry

Date 2023 Sep 18

PMID 37721707

Authors

Aparna Raj

Riju K Thomas

L Vidya

S Neelima

V M Aparna

C Sudarsanakumar

Affiliations

Soon will be listed here.

Abstract

Natural drug functionalised silver (Ag) nanoparticles (NPs) have gained significant interest in pharmacology related applications due to their therapeutic efficiency. We have synthesised silver nanoparticle using hesperetin as a reducing and capping agent. This work aims to discuss the relevance of the hesperetin functionalised silver nanoparticles (H-AgNPs) in the field of nano-medicine. The article primarily investigates the anticancer activity of H-AgNPs and then their interactions with calf thymus DNA (ctDNA) through spectroscopic and thermodynamic techniques. The green synthesised H-AgNPs are stable, spherical in shape and size of 10 ± 3 nm average diameter. The complex formation of H-AgNPs with ctDNA was established by UV-Visible absorption, fluorescent dye displacement assay, isothermal calorimetry and viscosity measurements. The binding constants obtained from these experiments were consistently in the order of 10 Mol. The melting temperature analysis and FTIR measurements confirmed that the structural alterations of ctDNA by the presence of H-AgNPs are minimal. All the thermodynamic variables and the endothermic binding nature were acquired from ITC experiments. All these experimental outcomes reveal the formation of H-AgNPs-ctDNA complex, and the results consistently verify the minor groove binding mode of H-AgNPs. The binding constant and limit of detection of 1.8 μM found from the interaction studies imply the DNA detection efficiency of H-AgNPs. The cytotoxicity of H-AgNPs against A549 and L929 cell lines were determined by in vitro MTT cell viability assay and lactate dehydrogenase (LDH) assay. The cell viability and LDH enzyme release are confirmed that the H-AgNPs has high anticancer activity. Moreover, the calculated LD50 value for H-AgNPs against lung cancer cells is 118.49 µl/ml, which is a low value comparing with the value for fibroblast cells (269.35 µl/ml). In short, the results of in vitro cytotoxicity assays revealed that the synthesised nanoparticles can be considered in applications related to cancer treatments. Also, we have found that, H-AgNPs is a minor groove binder, and having high DNA detection efficiency.

References

Shan X, Diez-Perez I, Wang L, Wiktor P, Gu Y, Zhang L . Imaging the electrocatalytic activity of single nanoparticles. Nat Nanotechnol. 2012; 7(10):668-72. DOI: 10.1038/nnano.2012.134. View

Li X, Khorsandi S, Wang Y, Santelli J, Huntoon K, Nguyen N . Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles. Nat Nanotechnol. 2022; 17(8):891-899. PMC: 9378430. DOI: 10.1038/s41565-022-01134-z. View

Gong N, Zhang Y, Teng X, Wang Y, Huo S, Qing G . Proton-driven transformable nanovaccine for cancer immunotherapy. Nat Nanotechnol. 2020; 15(12):1053-1064. PMC: 7719078. DOI: 10.1038/s41565-020-00782-3. View

Yeh Y, Creran B, Rotello V . Gold nanoparticles: preparation, properties, and applications in bionanotechnology. Nanoscale. 2011; 4(6):1871-80. PMC: 4101904. DOI: 10.1039/c1nr11188d. View

Christian P, von der Kammer F, Baalousha M, Hofmann T . Nanoparticles: structure, properties, preparation and behaviour in environmental media. Ecotoxicology. 2008; 17(5):326-43. DOI: 10.1007/s10646-008-0213-1. View

Xu L, Ma W, Wang L, Xu C, Kuang H, Kotov N . Nanoparticle assemblies: dimensional transformation of nanomaterials and scalability. Chem Soc Rev. 2013; 42(7):3114-26. DOI: 10.1039/c3cs35460a. View

Xu L, Wang Y, Huang J, Chen C, Wang Z, Xie H . Silver nanoparticles: Synthesis, medical applications and biosafety. Theranostics. 2020; 10(20):8996-9031. PMC: 7415816. DOI: 10.7150/thno.45413. View

Desireddy A, Conn B, Guo J, Yoon B, Barnett R, Monahan B . Ultrastable silver nanoparticles. Nature. 2013; 501(7467):399-402. DOI: 10.1038/nature12523. View

Yang H, Wang Y, Chen X, Zhao X, Gu L, Huang H . Plasmonic twinned silver nanoparticles with molecular precision. Nat Commun. 2016; 7:12809. PMC: 5023969. DOI: 10.1038/ncomms12809. View

10.

Skora B, Krajewska U, Nowak A, Dziedzic A, Barylyak A, Kus-Liskiewicz M . Noncytotoxic silver nanoparticles as a new antimicrobial strategy. Sci Rep. 2021; 11(1):13451. PMC: 8242066. DOI: 10.1038/s41598-021-92812-w. View

11.

Lem K, Choudhury A, Lakhani A, Kuyate P, Haw J, Lee D . Use of nanosilver in consumer products. Recent Pat Nanotechnol. 2011; 6(1):60-72. DOI: 10.2174/187221012798109318. View

12.

Dos Santos C, Seckler M, Ingle A, Gupta I, Galdiero S, Galdiero M . Silver nanoparticles: therapeutical uses, toxicity, and safety issues. J Pharm Sci. 2014; 103(7):1931-1944. DOI: 10.1002/jps.24001. View

13.

Mishra S, Singh B, Naqvi A, Singh H . Potential of biosynthesized silver nanoparticles using Stenotrophomonas sp. BHU-S7 (MTCC 5978) for management of soil-borne and foliar phytopathogens. Sci Rep. 2017; 7:45154. PMC: 5366874. DOI: 10.1038/srep45154. View

14.

Raj A, Thomas R, Vidya L, Aparna V, Neelima S, Sudarsanakumar C . Exploring the cytotoxicity on human lung cancer cells and DNA binding stratagem of camptothecin functionalised silver nanoparticles through multi-spectroscopic, and calorimetric approach. Sci Rep. 2023; 13(1):9045. PMC: 10239481. DOI: 10.1038/s41598-023-34997-w. View

15.

Fahmy H, Mosleh A, Elghany A, Shams-Eldin E, Abu Serea E, Ali S . Coated silver nanoparticles: synthesis, cytotoxicity, and optical properties. RSC Adv. 2022; 9(35):20118-20136. PMC: 9065456. DOI: 10.1039/c9ra02907a. View

16.

Khan A, Ikram M, Hahm J, Kim M . Antioxidant and Anti-Inflammatory Effects of Flavonoid Hesperetin: Special Focus on Neurological Disorders. Antioxidants (Basel). 2020; 9(7). PMC: 7402130. DOI: 10.3390/antiox9070609. View

17.

Sohel M, Sultana H, Sultana T, Al Amin M, Aktar S, Ali M . Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review. Heliyon. 2022; 8(1):e08815. PMC: 8810372. DOI: 10.1016/j.heliyon.2022.e08815. View

18.

Kanaze F, Bounartzi M, Georgarakis M, Niopas I . Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr. 2006; 61(4):472-7. DOI: 10.1038/sj.ejcn.1602543. View

19.

Erlund I, Silaste M, Alfthan G, Rantala M, Kesaniemi Y, Aro A . Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables. Eur J Clin Nutr. 2002; 56(9):891-8. DOI: 10.1038/sj.ejcn.1601409. View

20.

Takumi H, Nakamura H, Simizu T, Harada R, Kometani T, Nadamoto T . Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites. Food Funct. 2012; 3(4):389-98. DOI: 10.1039/c2fo10224b. View