Abstract
Background: Triple-Negative Breast Cancer (TNBC) presents a significant challenge due to its aggressive nature and lack of responsive hormone receptors, predominantly affecting younger premenopausal women. Ethyl ferulate (EF), a notable phytochemical, has demonstrated promising anti-cancer properties. This study aimed to enhance the efficacy of EF by synthesizing and characterizing ethyl ferulate gold nanoparticles (EF-AuNps) to passively target TNBC cells via the enhanced permeability and retention (EPR) effect.
Methods: We synthesized EF-AuNps using a direct reduction method and characterized the NPs by employing various techniques, including UV-visible spectroscopy, DLS, XRD, EDX, TEM, and FT-IR. The anti-proliferative activity against MDA-MB-231 cells was assessed using MTT and colony formation assays, alongside evaluating cell viability with PI-FACS and live/dead assays. Furthermore, a Western blot was performed to determine the mechanism of action of EFAuNps in TNBC cells.
Result: We successfully synthesized triangular EF-AuNps (<100nm) and observed a substantial inhibition of cell proliferation (IC50 18μg/ml). Compared to EF alone, EF-AuNps significantly enhanced cell death in TNBC cells, as confirmed by flow cytometry and viability assays. Besides, Western blot analysis verified that the expression of apoptotic-related signal proteins, such as survivin, caspase 3, and caspase 9, were modulated by EF-AuNps.
Conclusion: EF-AuNps showed higher anti-cancer efficacy than EF in the MDA-MB-231 cell line. These findings suggest the therapeutic potential of EF-AuNps for TNBC treatment, advocating for further preclinical and clinical investigations into this promising anti-cancer formulation.
Keywords: Gold nanoparticles, phytochemicals, ethyl ferulate, triple-negative breast cancer.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.2741/4844] [PMID: 32114421]
[http://dx.doi.org/10.1186/s13046-019-1443-1] [PMID: 31661003]
[http://dx.doi.org/10.1515/med-2020-0138] [PMID: 33336070]
[http://dx.doi.org/10.3390/cancers12040916] [PMID: 32276534]
[http://dx.doi.org/10.1002/jcp.30463] [PMID: 34105151]
[http://dx.doi.org/10.1016/j.jconrel.2020.07.003] [PMID: 32653502]
[http://dx.doi.org/10.12688/f1000research.18888.1] [PMID: 31448088]
[http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0465] [PMID: 32587770]
[http://dx.doi.org/10.1016/j.lfs.2020.118814] [PMID: 33333052]
[http://dx.doi.org/10.1089/jmf.2017.3930] [PMID: 28850308]
[http://dx.doi.org/10.3389/fonc.2021.650603] [PMID: 34660256]
[http://dx.doi.org/10.1016/j.crphar.2020.100008] [PMID: 34909644]
[http://dx.doi.org/10.3390/molecules24040734] [PMID: 30781671]
[http://dx.doi.org/10.1016/j.phymed.2017.07.001] [PMID: 28899496]
[http://dx.doi.org/10.1111/bph.13621] [PMID: 27638428]
[http://dx.doi.org/10.3390/ijms20174101] [PMID: 31443458]
[http://dx.doi.org/10.1021/acsptsci.1c00017] [PMID: 33860191]
[http://dx.doi.org/10.1002/ptr.7264] [PMID: 34498308]
[http://dx.doi.org/10.1016/j.jff.2021.104660]
[http://dx.doi.org/10.1016/j.lfs.2021.119201] [PMID: 33607159]
[http://dx.doi.org/10.1002/iub.2522] [PMID: 34170599]
[http://dx.doi.org/10.3389/fphar.2016.00003] [PMID: 26858645]
[http://dx.doi.org/10.3390/biom9010013] [PMID: 30609771]
[http://dx.doi.org/10.3858/emm.2011.43.12.078] [PMID: 21975281]
[http://dx.doi.org/10.1016/j.fct.2013.12.024] [PMID: 24373826]
[http://dx.doi.org/10.1021/jf304076z] [PMID: 23157164]
[http://dx.doi.org/10.1080/13543776.2019.1568410]
[http://dx.doi.org/10.1016/j.msec.2020.111057] [PMID: 32600687]
[http://dx.doi.org/10.1111/jfbc.13607] [PMID: 33587296]
[http://dx.doi.org/10.1093/cdn/nzab037_015]
[http://dx.doi.org/10.1016/j.biotechadv.2016.04.002] [PMID: 27071534]
[http://dx.doi.org/10.2174/1389200219666180918111528] [PMID: 30227814]
[http://dx.doi.org/10.1038/nrc.2016.108] [PMID: 27834398]
[http://dx.doi.org/10.1039/D0TB00957A] [PMID: 33026383]
[http://dx.doi.org/10.1016/j.nano.2021.102504] [PMID: 34890821]
[http://dx.doi.org/10.1039/D1NR04411G] [PMID: 34913453]
[http://dx.doi.org/10.3389/fnano.2021.694838]
[http://dx.doi.org/10.1016/j.addr.2018.07.007] [PMID: 30009886]
[http://dx.doi.org/10.1016/j.canlet.2014.02.006] [PMID: 24556077]
[http://dx.doi.org/10.1002/anie.200700465] [PMID: 17591736]
[http://dx.doi.org/10.1002/smll.200400093] [PMID: 17193451]
[http://dx.doi.org/10.1259/bjr/59448833] [PMID: 22010024]
[http://dx.doi.org/10.1038/aps.2011.82] [PMID: 21743485]
[http://dx.doi.org/10.1039/c2nr33776b] [PMID: 23348618]
[http://dx.doi.org/10.1016/j.colsurfb.2009.09.008] [PMID: 19815393]
[http://dx.doi.org/10.1007/s00449-010-0510-y] [PMID: 21229266]
[http://dx.doi.org/10.1007/s11051-010-9911-8] [PMID: 21170131]
[http://dx.doi.org/10.1039/B514191E] [PMID: 16505915]
[http://dx.doi.org/10.1016/j.lfs.2020.118475] [PMID: 32976884]
[http://dx.doi.org/10.1021/acsptsci.1c00011] [PMID: 33860206]
[http://dx.doi.org/10.1007/s12668-015-0185-6]
[http://dx.doi.org/10.1016/j.saa.2013.03.076] [PMID: 23624042]
[http://dx.doi.org/10.1016/j.colsurfb.2008.09.021] [PMID: 18977643]
[http://dx.doi.org/10.1166/nnl.2013.1678]
[http://dx.doi.org/10.1016/j.clbc.2017.07.013] [PMID: 28801156]
[http://dx.doi.org/10.1182/blood-2007-01-067256] [PMID: 17332240]
[http://dx.doi.org/10.1016/j.phymed.2016.12.002] [PMID: 28190465]
[http://dx.doi.org/10.1016/j.phymed.2015.08.015] [PMID: 26598915]
[http://dx.doi.org/10.3389/fphar.2018.00686] [PMID: 30127736]
[http://dx.doi.org/10.1016/j.jff.2018.12.020]
[http://dx.doi.org/10.2174/1381612822666160609110231] [PMID: 27291284]
[http://dx.doi.org/10.1016/j.phrs.2020.104635] [PMID: 31926274]
[http://dx.doi.org/10.3390/molecules25102278] [PMID: 32408623]
[http://dx.doi.org/10.1016/j.lfs.2020.118182] [PMID: 32781063]
[http://dx.doi.org/10.1002/pros.20899] [PMID: 19107816]
[http://dx.doi.org/10.2174/1574892810666151020101706] [PMID: 26537958]
[http://dx.doi.org/10.31557/APJCP.2019.20.11.3437] [PMID: 31759370]
[http://dx.doi.org/10.1007/s11010-013-1732-5] [PMID: 23807740]
[http://dx.doi.org/10.1002/ptr.7082] [PMID: 33749909]
[http://dx.doi.org/10.1016/j.etap.2013.03.023] [PMID: 23628949]
[http://dx.doi.org/10.1016/j.etap.2013.12.004] [PMID: 24384279]
[http://dx.doi.org/10.2174/138955711796575489] [PMID: 21762105]
[http://dx.doi.org/10.3762/bjoc.10.241] [PMID: 25298799]
[http://dx.doi.org/10.1038/nmat1152] [PMID: 15208703]
[http://dx.doi.org/10.1016/j.colsurfb.2010.08.036] [PMID: 20833002]
[http://dx.doi.org/10.1016/j.saa.2012.09.042] [PMID: 23211617]
[http://dx.doi.org/10.6028/NIST.SP.1200-26]
[http://dx.doi.org/10.1186/1556-276X-9-627] [PMID: 25489281]
[http://dx.doi.org/10.4103/0971-5916.159250] [PMID: 26112839]
[http://dx.doi.org/10.1016/j.fbio.2021.101340]
[http://dx.doi.org/10.1016/j.jddst.2021.102665]