Synthesis, characterization and in vitro study of biocompatible cinnamaldehyde functionalized magnetite nanoparticles (CPGF Nps) for hyperthermia and drug delivery applications in breast cancer
Authors: Rajeev C Chikate
Ruchika Kaul-Ghanekar
Avinash V Deore
Sanjay D Dhole
Brijesh S Kadu
Pankaj Poddar
Preeti Gupta
Prakash Mansara
Kirtee D Wani
Journal: PloS one (2014)
Discipline: Multidisciplinary
Keywords: Cinnamaldehyde; Fe3O4 nanoparticles; drug delivery; hyperthermia; breast cancer
Affiliations: Cell and Translational Research Laboratory, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth University Medical College Campus, Dhankawadi, Pune, Maharashtra, India., Nanoscience Group, Department of Chemistry, Post-graduate and Research Center, MES Abasaheb Garware College, Pune, Maharashtra, India., Physical and Material Chemistry Division, CSIR-National Chemical Laboratory, Pune, Maharashtra, India., Department of Physics, University of Pune, Pune, Maharashtra, India.

Abstract:  Cinnamaldehyde, the bioactive component of the spice cinnamon, and its derivatives have been shown to possess anti-cancer activity against various cancer cell lines. However, its hydrophobic nature invites attention for efficient drug delivery systems that would enhance the bioavailability of cinnamaldehyde without affecting its bioactivity. Here, we report the synthesis of stable aqueous suspension of cinnamaldehyde tagged Fe3O4 nanoparticles capped with glycine and pluronic polymer (CPGF NPs) for their potential application in drug delivery and hyperthermia in breast cancer. The monodispersed superparamagnetic NPs had an average particulate size of ∼ 20 nm. TGA data revealed the drug payload of ∼ 18%. Compared to the free cinnamaldehyde, CPGF NPs reduced the viability of breast cancer cell lines, MCF7 and MDAMB231, at lower doses of cinnamaldehyde suggesting its increased bioavailability and in turn its therapeutic efficacy in the cells. Interestingly, the NPs were non-toxic to the non-cancerous HEK293 and MCF10A cell lines compared to the free cinnamaldehyde. The novelty of CPGF nanoparticulate system was that it could induce cytotoxicity in both ER/PR positive/Her2 negative (MCF7) and ER/PR negative/Her2 negative (MDAMB231) breast cancer cells, the latter being insensitive to most of the chemotherapeutic drugs. The NPs decreased the growth of the breast cancer cells in a dose-dependent manner and altered their migration through reduction in MMP-2 expression. CPGF NPs also decreased the expression of VEGF, an important oncomarker of tumor angiogenesis. They induced apoptosis in breast cancer cells through loss of mitochondrial membrane potential and activation of caspase-3. Interestingly, upon exposure to the radiofrequency waves, the NPs heated up to 41.6 °C within 1 min, suggesting their promise as a magnetic hyperthermia agent. All these findings indicate that CPGF NPs prove to be potential nano-chemotherapeutic agents in breast cancer. 

Retracted: No

PubPeer comments:
 ![file] Two upper patterns and two bottom patterns are identical. , 
 #1 Vertically compressing the XRD for  F by 50% gives us the smoothed  GF pattern. Most of the noise is the same, but in places the noise spikes for  GF seem to have been clipped. ![file] How does a clipped version of the noisy signal produce the same smoothed version? , 
 #1 Even better - they are all the same curve with different vertical squeezing stretching (don t know which is the original). ![file] , 
 u2022tThe figure 1A indicates powder diffraction patterns of F, GF, PGF and CPGF NPs. These compositions exhibited characteristic magnetite peaks (2u03b8) at 30.1, 36.2, 42.4,52.5, 57.5 and 62.2u00b0 corresponding to (220), (311), (400), (422),(511) and (440) planes, respectively (JCPDS card no. 01-088-0315), observed for face centered cubic (fcc) lattice structure of iron oxide. u2022tUpon processing for smoothening and for stacking, all the patterns looked similar which indicated that the crystalline structure of Fe3O4 remained same even after the surface modification with glycine, pluronic F127 and cinnamaldehyde. u2022tVarious references (given below) show similar XRD patterns even after surface modification with different moieties. Supporting References:t 1.tIrshad Ahmad I, Siddiqui W, Ahmad T (2019) Synthesis and characterization of molecularly imprinted magnetite nanomaterials as a novel adsorbent for the removal of heavy metals from aqueous solution. J Mater Res Technol 8(5):4239u20134252. 2.tLu W, Ling M, Jia M, Huang P, Li C, Yan B (2014) Facile synthesis and characterization of polyethylenimine-coated Fe3O4 superparamagnetic nanoparticles for cancer cell separation. Molecular Medicine Reports 9: 1080-1084. 3.tShi SF, Jia JF, Guo XK, Zhao YP, et al. Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast cells. International Journal of Nanomedicine7: 5593u20135602. 4.tWei Y, Han B, Hu X, Lin Y, Wang X, Deng X (2012) Synthesis of Fe3O4 nanoparticles and their magnetic properties. Procedia Engineering 27: 632 u2013 637. ,