Synthesis of composite magnetic nanoparticles Fe3O4with alendronate for osteoporosis treatment.
Osteoporosis is a result of imbalance between bone formation by osteoblasts and resorption by osteoclasts (OCs). In the present study, we investigated the potential of limiting the aggravation of osteoporosis by reducing the activity of OCs through thermolysis. The proposed method is to synthesize bisphosphonate (Bis)-conjugated iron (II, III) oxide (Fe3O4) nanoparticles and incorporate them into OCs. The cells should be subsequently exposed to radiofrequency (RF) to induce thermolysis. In this study, particles of Fe3O4were first synthesized by chemical co-precipitation and then coated with dextran (Dex). The Dex/Fe3O4particles were then conjugated with Bis to form Bis/Dex/Fe3O4. Transmission electron microscopy revealed that the average diameter of the Bis/Dex/Fe3O4particles was ~20 nm. All three kinds of nanoparticles were found to have cubic inverse spinel structure of Fe3O4by the X-ray diffraction analysis. Fourier transform infrared spectroscopy confirmed that the Dex/Fe3O4and Bis/Dex/Fe3O4nanoparticles possessed their respective Dex and Bis functional groups, while a superconducting quantum interference device magnetometer measured the magnetic moment to be 24.5 emu. In addition, the Bis/Dex/Fe3O4nanoparticles were fully dispersed in double-distilled water. Osteoblasts and OCs were individually cultured with the nanoparticles, and an MTT assay revealed that they were non-cytotoxic. An RF system (42 kHz and 450 A) was used to raise the temperature of the nanoparticles for 20 minutes, and the thermal effect was found to be sufficient to destroy OCs. Furthermore, in vivo studies verified that nanoparticles were indeed magnetic resonance imaging contrast agents and that they accumulated after being injected into the body of rats. In conclusion, we developed a water-dispersible magnetic nanoparticle that had RF-induced thermogenic properties, and the results indicated that the Bis/Dex/Fe3O4nanoparticle had the potential for controlling osteoporosis.
Department of Biomedical Engineering; Department of Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan.
Ming-Song
MS
Lee
Department of Biomedical Engineering.
Chao-Ming
CM
Su
Department of Biomedical Engineering; Institute of Urology, University of Southern California, Los Angeles, CA, USA.
Jih-Chao
JC
Yeh
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Pei-Ru
PR
Wu
Department of Biomedical Engineering.
Tien-Yao
TY
Tsai
Department of Biomedical Engineering; Department of Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan.
Shyh-Liang
SL
Lou
D019386:Alendronate / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D011232:Chemical Precipitation; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D052203:Ferrosoferric Oxide / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014961:X-Ray Diffraction
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D019386:Alendronate; D052203:Ferrosoferric Oxide
bisphosphonate; iron oxide; radiofrequency; thermolysis; thermotherapy
Adv Drug Deliv Rev. 2010 Aug 30;62(11):1064-79
20691229
Mayo Clin Proc. 2008 Sep;83(9):1032-45
18775204
Expert Opin Drug Deliv. 2007 Nov;4(6):621-33
17970665
N Engl J Med. 1995 Nov 30;333(22):1437-43
7477143
Ophthalmology. 1999 Oct;106(10):1908-14
10519584
Angew Chem Int Ed Engl. 2007;46(8):1222-44
17278160
Biochem Pharmacol. 1990 Nov 15;40(10):2353-62
2244936
Nanomedicine. 2015 Feb;11(2):313-27
25461284
J Neurooncol. 2007 Jan;81(1):53-60
16773216
N Engl J Med. 2000 Aug 31;343(9):604-10
10979796
Clin Ther. 2012 Mar;34(3):521-36
22440513
J Neurooncol. 2006 May;78(1):7-14
16314937
N Engl J Med. 2009 Jan 1;360(1):53-62
19118304
Pharmacol Res. 2010 Aug;62(2):126-43
20044004
J Am Chem Soc. 2006 Jun 7;128(22):7383-9
16734494
J Bone Miner Res. 1994 Aug;9(8):1137-41
7976495
N Engl J Med. 1993 Jun 17;328(24):1747-52
7684512
N Engl J Med. 1995 Feb 2;332(5):305-11
7816067
Int J Radiat Oncol Biol Phys. 1996 Jul 1;35(4):731-44
8690639
Oral Dis. 2002 May;8(3):147-59
12108759
Int J Oncol. 2000 Jun;16(6):1153-8
10811989
J Urol. 1993 Nov;150(5 Pt 2):1591-6
7692092
Am J Gastroenterol. 2000 Mar;95(3):634-40
10710050
Bone. 2000 Jul;27(1):119-22
10865218
Am J Gastroenterol. 1996 Jun;91(6):1282-3
8651202
Maturitas. 2004 Jul 15;48(3):243-51
15207890
Clin Chim Acta. 2011 Nov 20;412(23-24):2146-9
21839730
Int J Hyperthermia. 1997 Nov-Dec;13(6):587-605
9421741
Bone. 2010 Apr;46(4):935-9
20060081
N Engl J Med. 2004 Mar 18;350(12 ):1189-99
15028823
J Trace Elem Med Biol. 2012 Jun;26(2-3):153-6
22565017
Biomaterials. 2005 Jun;26(18):3995-4021
15626447
J Nanosci Nanotechnol. 2007 Dec;7(12):4604-6
18283851