Macrophages as immunocyte are attracting more and more attention in cancer therapy. Our previous study observed that dimercaptosuccinic acid (DMSA)-coated Fe3O4 magnetic nanoparticles triggered comprehensive immune responses of mouse macrophages (RAW264.7 cells) and induced production of many kinds of cytokines. This study investigated the effects of Fe3O4 magnetic nanoparticles on RAW264.7 cells proliferation, migration, and inhibition of tumor growth in vitro. Fe3O4 magnetic nanoparticles had an average size of about 11 nm with good dispersibility and uniformity. Fe3O4 magnetic nanoparticles internalized efficiently into RAW264.7 cells. Through Cell Counting Kit-8 (CCK-8) detection, the proliferation of RAW264.7 cells significantly increased by the low-dose Fe3O4 magnetic nanoparticles (50 µg/mL) treatment. The results of wound-healing and Transwell assays both displayed a significant promotion of the RAW264.7 cells migratory capability compared with control group (P<0.01). It is interesting to find that a large number of proliferated RAW264.7 cells were activated to surround quickly and attack mouse liver cancer cell (Hepa1-6) cells by Fe3O4 magnetic nanoparticles. The growth of Hepa1-6 cells was effectively inhibited according to microscope imaging and flow cytometry analysis. The inhibition may be cooperative effects of RAW264.7 cells proliferation, migration, and immune activation. The results suggest potential clinical value of low-dose iron oxide nanomaterials in cancer therapy.
EnukashvilyNLevchukKBagaevaVVet al.
91 – Uncoated iron oxide nanoparticles as a tool for human mesenchymal stromal cells labelling in vivo. Cytotherapy. 2018;
20: S36.
2.
Jasmin de SouzaGTLouzadaRAet al.
Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations. Int J Nanomed2017;
12: 779–793.
3.
JunejaRRoyI.Iron oxide-doped niosomes as drug carriers for magnetically targeted drug delivery. Int J Nanomed2018;
13: 7–9.
4.
El-BoubbouK.Magnetic iron oxide nanoparticles as drug carriers: clinical relevance. Nanomedicine2018; 13: 953–971.
5.
HuangYMaoKZhangBet al.
Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics. Mater Sci Eng C2017;
70: 763–771.
6.
WinterAChavanAWawroschekF.Magnetic resonance imaging of sentinel lymph nodes using intraprostatic injection of superparamagnetic iron oxide nanoparticles in prostate cancer patients: first-in-human results. Eur Urol2018;
73: 813–814.
7.
VitalianoGKimJMintzopoulosDet al.
S262. Novel targeted clathrin-based superparamagnetic iron oxide nanoparticles for CNS magnetic resonance imaging of dopamine transporters. Biol Psychiatry2018;
83: S450.
8.
HachaniRBirchallMALowdellMWet al.
Assessing cell-nanoparticle interactions by high content imaging of biocompatible iron oxide nanoparticles as potential contrast agents for magnetic resonance imaging. Scient Rep2017;
7: 7850.
9.
NosratiHSalehiabarMAttariEet al.Green and one-pot surface coating of iron oxide magnetic nanoparticles with natural amino acids and biocompatibility investigation. Appl Organometal Chem2017;
32: 1–10.
10.
NosratiHSalehiabarMHamidrezaMKet al.Theranostic nanoparticles based on magnetic nanoparticles: design, preparation, characterization and evaluation as novel anticancer drug carrier and MRI contrast agent. Drug Dev Ind Pharm2018;
44: 1–29.
11.
NosratiHAdibtabarMSharafiAet al.
PAMAM-modified citric acid-coated magnetic nanoparticles as pH sensitive biocompatible carrier against human breast cancer cells. Drug Dev Ind Pharm2018;
44: 1–27.
12.
NosratiHSalehiabarMDavaranSet al.Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells. Drug Dev Ind Pharm 2018; 44: 886–894.
13.
NosratiHMojtahediADanafarHet al.Enzymatic stimuli-responsive methotrexate-conjugated magnetic nanoparticles for target delivery to breast cancer cells and release study in lysosomal condition. J Biomed Mater Res A2018;
106: 1646–1654.
14.
NosratiHHamzeheiHAfrooghSet al.Phenyl alanine & tyrosine amino acids coated magnetic nanoparticles: preparation and toxicity study. Drug Res2018; 8: 1–7.
15.
NosratiHSalehiabarMManjiliHKet al.Preparation of magnetic albumin nanoparticles via a simple and one-pot desolvation and co-precipitation method for medical and pharmaceutical applications. Int J Biol Macromol2017; 108: 909–915.
16.
ZhaoZZhouZBaoJet al.
Octapod iron oxide nanoparticles as high-performance T2 contrast agents for magnetic resonance imaging. Nat Commun2018;
4: 2266.
17.
LeeSThomasRGMoonMJet al.Near-infrared heptamethine cyanine based iron oxide nanoparticles for tumor targeted multimodal imaging and photothermal therapy. Scient Rep2017;
7: 2018.
18.
ZanganehSHutterGSpitlerRet al.
Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nature Nanotechnol2016;
11: 986–994.
19.
ZhangLChenYWuLet al.
Effects of iron nanoparticles on immune response of two immunocytes like virus. Nanosci Nanotechnol Lett2017;
9: 1934–1946.
20.
MantovaniAAllavenaP.The interaction of anticancer therapies with tumor-associated macrophages. J Exp Med2015;
212: 1–11.
21.
FranklinRALiaoWSarkarAet al.
The cellular and molecular origin of tumor-associated macrophages. Science2014;
344: 921–925.
22.
O’SullivanTSaddawikonefkaRVermiWet al.
Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J Exp Med2012;
209: 1869–1882.
23.
BiswasSKMantovaniA.Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol2010;
11: 889–896.
24.
HeadleyMBBinsANipAet al.
Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature2016;
531: 513–519.
25.
ChistiakovDAMyasoedovaVARevinVVet al.
The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobiology2018;
223: 101–111.
26.
KlarASMichalakmićkaKBiedermannTet al.
Characterization of M1 and M2 polarization of macrophages in vascularized human dermo-epidermal skin substitutes in vivo. Pediatr Surg Int2018;
34: 1–7.
ChenZPZhangYZhangSet al.
Preparation and characterization of water-soluble monodisperse magnetic iron oxide nanoparticles via surface double-exchange with DMSA. Colloid Surf A2008;
316: 210–216.
29.
LiuYWangJ.Effects of DMSA-coated Fe3O4 nanoparticles on the transcription of genes related to iron and osmosis homeostasis. Toxicol Sci2013;
131: 521–536.
30.
MagroMBaratellaDBonaiutoEet al.
New perspectives on biomedical applications of iron oxide nanoparticles. Curr Med Chem2018;
25: 540–555.
31.
ZhangLWangXZouJet al.
Effects of an 11-nm DMSA-coated iron nanoparticle on the gene expression profile of two human cell lines, THP-1 and HepG2. J Nanobiotechnol2015;
13: 1–17.
32.
SunQKanehiraKTaniguchiA.Low doses of TiO2-polyethylene glycol nanoparticles stimulate proliferation of hepatocyte cells. Sci Technol Adv Mater2016;
17: 669–676.
GutweinLGWebsterTJ.Osteoblast and chrondrocyte proliferation in the presence of alumina and titania nanoparticles. J Nanopart Res2002;
4: 231–238.
35.
HouRNieLDuGet al.
Natural polysaccharides promote chondrocyte adhesion and proliferation on magnetic nanoparticle/PVA composite hydrogels. Colloid Surf B2015;
132: 146–154.
36.
LiCLiZWangYet al.
Gold nanoparticles promote proliferation of human periodontal ligament stem cells and have limited effects on cells differentiation. J Nanomater2016;
2016: 1–10.
37.
AramiHKhandharALiggittDet al.
In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles. Chem Soc Rev2015;
44: 8576–8607.
38.
YuZZWuQHZhangSLet al.
Two novel amino acid-coated super paramagnetic nanoparticles at low concentrations label and promote the proliferation of mesenchymal stem cells. RSC Adv2016;
6: 10159–10161.
39.
Aydemir SezerUOzturkKAruBet al.
Zero valent zinc nanoparticles promote neuroglial cell proliferation: a biodegradable and conductive filler candidate for nerve regeneration. J Mater Sci Mater Med2016;
28: 1–11.
40.
DykmanLAKhlebtsovNG.Immunological properties of gold nanoparticles. Chem Sci2017;
8: 1719–1735.
41.
BancosSTsaiDHHackleyVet al.
Evaluation of viability and proliferation profiles on macrophages treated with silica nanoparticles in vitro via plate-based, flow cytometry, and coulter counter assays. ISRN Nanotechnol2012;
2012: 1–11.
42.
CaiYLiuYYanWet al.
Role of hydroxyapatite nanoparticle size in bone cell proliferation. J Mater Chem2007;
17: 3780–3787.
43.
LiuYChenZGuNet al.
Effects of DMSA-coated Fe3O4 magnetic nanoparticles on global gene expression of mouse macrophage RAW264.7 cells. Toxicol Lett2011;
205: 130–139.
44.
LuoYPollardJWCasadevallA.Fcgamma receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway. J Biol Chem2010;
285: 4232–4242.
45.
VeisehOGunnJWKievitFMet al.
Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. Small (Weinheim an der Bergstrasse, Germany)2009;
5: 256–264.
46.
TranTAKrishnamoorthyKChoSKet al.
Inhibitory effect of zinc sulfide nanoparticles towards breast cancer stem cell migration and invasion. J Biomed Nanotechnol2016;
12: 329–336.
47.
AliliLSackMvon MontfortCet al.
Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid Redox Signal2013;
19: 765–778.
48.
GallantBPClarkMMadiganAet al.
Nanoparticles mimic exosomes and attenuate growth factor-induced cell migration in melanoma cells. FASEB J2017;
31: 614–617.
49.
SongYJinJLiJet al.
Gd@C82(OH)22 nanoparticles constrain macrophages migration into tumor tissue to prevent metastasis. J Nanosci Nanotechnol2014;
14: 4022–4028.
50.
LiuZWuYGuoZet al.
Effects of internalized gold nanoparticles with respect to cytotoxicity and invasion activity in lung cancer cells. Plos One2014;
9: e99175.
51.
ChangYNGuoHLiJet al.
Adjusting the balance between effective loading and vector migration of macrophage vehicles to deliver nanoparticles. PLoS One2013;
8: e76024.
52.
LiuYZouJWangXet al.
Effects of 2,3-dimercaptosuccinic acid-coated Fe3O4 nanoparticles on genes in two mouse cell lines. J Biomed Nanotechnol2014;
10: 1574–1587.
53.
StoutRDJiangCMattaBet al.
Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol2005;
175: 342–349.
54.
LucarelliMGattiAMSavarinoGet al.
Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles. Eur Cytokine Netw2004;
15: 339–346.
55.
WangYLinYXQiaoSLet al.
Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment. Biomaterials2017;
112: 153–163.
56.
LeeJYParkWYiDK.Immunostimulatory effects of gold nanorod and silica-coated gold nanorod on RAW 264.7 mouse macrophages. Toxicol Lett2012;
209: 51–57.
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