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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

Synthesis and Characterization of Folic Acid Conjugated Gemcitabine Tethered Silver Nanoparticles (FA-GEM-AgNPs) for Targeted Delivery

Author(s): Arjunan Karuppaiah, Ravikumar Rajan, Sivaram Hariharan, Dinesh K. Balasubramaniam, Marslin Gregory* and Veintramuthu Sankar*

Volume 26, Issue 26, 2020

Page: [3141 - 3146] Pages: 6

DOI: 10.2174/1381612826666200316143239

Price: $65


Background: Silver nanoparticles (AgNPs) have attracted considerable interest in the medical industry due to their physicochemical properties, small size, and surface plasmon behavior. Their smaller particle size and instability in blood circulation leads to toxicity due to its aggregation as Ag+ ions and accumulation at the deepseated organ. In the present study, we aimed at reducing the toxicity of AgNPs by conjugation with an anticancer drug GEM and to improve their internalization through folate receptors-mediated endocytosis by capping the nanoparticles with folic acid (FA).

Methods: One-pot facile synthesis of FA capped silver nanoparticles (FA-AgNPs) has been achieved by using FA as a reducing agent. FA-AgNPs were mixed with Gemcitabine (GEM) to obtain tethered FA-GEM-AgNPs. Nanoparticles were characterized by Dynamic Light Scattering (DLS), UV-Visible spectroscopy, Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX), Selected Area Electron Diffraction (SAED), and Atomic Absorption Spectroscopy (AAS). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effect of the prepared nanoformulations. The apoptotic cell death induced by FA-GEM-AgNPs in breast cancer cells were monitored with Acridine orange (AO)/Ethidium Bromide (EtBr) staining.

Conclusion: Compared to GEM and AgNPs, FA-GEM-AgNPs showed enhanced cytotoxic effect and internalization in MDA-MB-453 breast cancer cell line. FA-GEM-AgNPs could be an ideal candidate for targeting cancer cells via folate receptor-mediated endocytosis.

Keywords: Breast cancer, silver nanoparticles, metallic nanoparticles, chemical reduction, folic acid reduction, gemcitabine, folate receptor, MDA-MB-453.

Glasgow MD, Chougule MB. Recent developments in active tumor targeted multifunctional nanoparticles for combination chemotherapy in cancer treatment and imaging. J Biomed Nanotechnol 2015; 11(11): 1859-98.
[] [PMID: 26554150]
Lombardo D, Kiselev MA, Caccamo MT. Smart nanoparticles for drug delivery application: development of versatile nanocarrier platforms in biotechnology and nanomedicine. J Nanomater 2019; 2019: 26.
Rao CN, Kulkarni GU, Thomas PJ, Edwards PP. Size-dependent chemistry: properties of nanocrystals. Chemistry 2002; 8(1): 28-35.
[<28:AID-CHEM28>3.0.CO;2-B] [PMID: 11826864]
Xiu ZM, Zhang QB, Puppala HL, Colvin VL, Alvarez PJ. Negligible particle-specific antibacterial activity of silver nanoparticles. Nano Lett 2012; 12(8): 4271-5.
[] [PMID: 22765771]
Asghari S, Johari SA, Lee JH, et al. Toxicity of various silver nanoparticles compared to silver ions in Daphnia magna. J Nanobiotechnology 2012; 10: 14.
[] [PMID: 22472056]
Vance ME, Kuiken T, Vejerano EP, et al. Nanotechnology in the real world: Redeveloping the nanomaterial consumer products inventory. Beilstein J Nanotechnol 2015; 6: 1769-80.
[] [PMID: 26425429]
Valenti LE, Giacomelli CE. Stability of silver nanoparticles: agglomeration and oxidation in biological relevant conditions. J Nanopart Res 2017; 19: 156.
Dziendzikowska K, Gromadzka-Ostrowska J, Lankoff A, et al. Time-dependent biodistribution and excretion of silver nanoparticles in male Wistar rats. J Appl Toxicol 2012; 32(11): 920-8.
[] [PMID: 22696427]
Marslin G, Selvakesavan RK, Franklin G, Sarmento B, Dias AC. Antimicrobial activity of cream incorporated with silver nanoparticles biosynthesized from Withania somnifera. Int J Nanomedicine 2015; 10: 5955-63.
[PMID: 26445537]
Tiwari DK, Jin T, Behari J. Dose-dependent in-vivo toxicity assessment of silver nanoparticle in Wistar rats. Toxicol Mech Methods 2011; 21(1): 13-24.
[] [PMID: 21080782]
Montalvo-Quiros S, Aragoneses-Cazorla G, Garcia-Alcalde L, Vallet-Regí M, González B, Luque-Garcia JL. Cancer cell targeting and therapeutic delivery of silver nanoparticles by mesoporous silica nanocarriers: insights into the action mechanisms using quantitative proteomics. Nanoscale 2019; 11(10): 4531-45.
[] [PMID: 30806414]
Zwicke GL, Mansoori GA, Jeffery CJ. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano Rev 2012; 3
[] [PMID: 23240070]
Bhanumathi R, Manivannan M, Thangaraj R, Kannan S. Drug-carrying capacity and anticancer effect of the folic acid- and berberine-loaded silver nanomaterial to regulate the akt-erk pathway in breast cancer. ACS Omega 2018; 3(7): 8317-28.
[] [PMID: 30087941]
Kayani Z, Bordbar A-K, Firuzi O. Novel folic acid-conjugated doxorubicin loaded β-lactoglobulin nanoparticles induce apoptosis in breast cancer cells. Biomed Pharmacother 2018; 107: 945-56.
[] [PMID: 30257407]
Yang R, An Y, Miao F, Li M, Liu P, Tang Q. Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo. Int J Nanomedicine 2014; 9: 4231-43.
[] [PMID: 25228802]
Cammarata CR, Hughes ME, Ofner CM III. Carbodiimide induced cross-linking, ligand addition, and degradation in gelatin. Mol Pharm 2015; 12(3): 783-93.
[] [PMID: 25658665]
Thulasidasan AKT, Retnakumari AP, Shankar M, et al. Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy. Oncotarget 2017; 8(64): 107374-89.
[] [PMID: 29296172]
Mulfinger L, Solomon SD, Bahadory M, Jeyarajasingam AV, Rutkowsky SA, Boritz C. Synthesis and study of silver nanoparticles. J Chem Educ 2007; 84: 322.
Rawat KA, Singhal RK, Kailasa SK. One-pot synthesis of silver nanoparticles using folic acid as a reagent for colorimetric and fluorimetric detections of 6-mercaptopurine at nanomolar concentration. Sens Actuators B Chem 2017; 249: 30-8.
Su D, Yang X, Xia Q, et al. Folic acid functionalized silver nanoparticles with sensitivity and selectivity colorimetric and fluorescent detection for Hg2+ and efficient catalysis. Nanotechnology 2014; 25(35)355702
[] [PMID: 25116278]
Noh HJ, Im AR, Kim HS, et al. Antibacterial activity and increased freeze-drying stability of sialyllactose-reduced silver nanoparticles using sucrose and trehalose. J Nanosci Nanotechnol 2012; 12(5): 3884-95.
[] [PMID: 22852321]
Hamarat Sanlıer S, Yasa M, Cihnioglu AO, Abdulhayoglu M, Yılmaz H, Ak G. Development of gemcitabine-adsorbed magnetic gelatin nanoparticles for targeted drug delivery in lung cancer. Artif Cells Nanomed Biotechnol 2016; 44(3): 943-9.
[PMID: 25615875]
Chowdhuri AR, Tripathy S, Haldar C, et al. Theoretical and experimental study of folic acid conjugated silver nanoparticles through electrostatic interaction for enhance antibacterial activity. RSC Advances 2015; 5: 21515-24.
Mirzaei A, Janghorban K, Hashemi B, Bonyani M, Leonardi SG, Neri G. Characterization and optical studies of PVP-capped silver nanoparticles. J Nanostructure Chem 2017; 7: 37-46.
Guzmán JDMG, Godet S. Synthesis of silver nanoparticles by chemical reduction method and their antibacterial activity. International J Mater Metallurgical Eng 2008; 2: 3.
Zielińska A, Skwarek E, Zaleska A, Gazda M, Hupka J. Preparation of silver nanoparticles with controlled particle size. Procedia Chem 2009; 1: 1560-6.
Agnihotri S, Mukherji S, Mukherji S. Size-controlled silver nanoparticles synthesized over the range 5-100 nm using the same protocol and their antibacterial efficacy. RSC Advances 2014; 4: 3974-83.
Park S, Chibli H, Wong J, Nadeau JL. Antimicrobial activity and cellular toxicity of nanoparticle-polymyxin B conjugates. Nanotechnology 2011; 22(18)185101
[] [PMID: 21415471]
Sooresh A, Kwon H, Taylor R, Pietrantonio P, Pine M, Sayes CM. Surface functionalization of silver nanoparticles: novel applications for insect vector control. ACS Appl Mater Interfaces 2011; 3(10): 3779-87.
[] [PMID: 21957003]
Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol 2011; 697: 63-70.
[] [PMID: 21116954]
Jiang L, Krasowska M, Fornasiero D, Koh P, Ralston J. Electrostatic attraction between a hydrophilic solid and a bubble. Phys Chem Chem Phys 2010; 12(43): 14527-33.
[] [PMID: 20931115]
Sambale F, Wagner S, Stahl F, Khaydarov RR, Scheper T, Bahnemann D. Investigations of the toxic effect of silver nanoparticles on mammalian cell lines. J Nanomater 2015; 2015: 9.
Banerjee PP, Bandyopadhyay A, Harsha SN, et al. Mentha arvensis (Linn.)-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells. Breast Cancer (Dove Med Press) 2017; 9: 265-78.
[] [PMID: 28458579]
Tambe P, Kumar P, Paknikar KM, Gajbhiye V. Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells. Int J Nanomedicine 2018; 13: 7669-80.
[] [PMID: 30538451]

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