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Gajendiran, Mani; Jo, Heejung; Kim, Kyobum; Balasubramanian, Sengottuvelan
International journal of nanomedicine, 01/2019, Volume: 14Journal Article
Background: Surface functionalization of gold nanoparticles (AuNPs) has emerged as a promising field of research with enormous biomedical applications. The folate (FA)-attached polymer-gold nanoconjugates play vital role in targeting the cancer cells. Methods: AuNPs were synthesized by using di- or tri-carboxylate-polyethylene glycol (PEG) polymers, including citrate-PEG (CPEG), malate-PEG (MAP), and tartrate-PEG (TAP), as a reducing and stabilizing agent. After synthesis of polymer-AuNPs, the freely available hydroxyl and carboxylate groups of CPEG, MAP, and TAP were used to attach a cancer cell- targeting agent, FA, via a 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxy succinimide coupling reaction to obtain FA-CPEG-AuNP, FA-MAP-AuNP, and FA-TAP-AuNP nanoconjugates, respectively. The 5-fluorouracil (5FU) was attached to pi back-bonded carbonyl oxygens of the nanoconjugates, and the in vitro drug release profile was studied by high pressure liquid chromatography. Biocompatibility profiles of the FA-CPEG-AuNP, FA-MAP-AuNP, and FATAP-AuNP nanoconjugates were investigated using adult human dermal fibroblasts. Anti- breast cancer activity of 5FU-loaded nanoconjugates was investigated using MCF-7 breast cancer cells. Results: X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy analyses confirmed that AuNPs attached to CPEG, MAP, or TAP via the formation of pi back bonding between AuNPs and the ester carbonyl group. The pi back-bonded nanoconjugates exhibited sustained release of 5FU up to 27 days. FA-MAP-AuNPs exhibited an IC.sub.50 at 5 microlg/mL, while FACPEG-AuNPs and FA-TAP-AuNPs showed the IC.sub.50 at 100 microg/mL toward MCF-7 cancer cells. Conclusion: The developed polymer pi back-bonded multifunctional gold nanoconjugates could be used as a potential drug delivery system for targeting MCF-7 cancer cells. Keywords: polymer-gold nanoconjugates, 5-fluorouracil, anticancer activity, MCF- 7 cells, green synthesis
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