Skip to main content
Erschienen in: Journal of Nanoparticle Research 10/2012

01.10.2012 | Research Paper

Methotrexate-conjugated magnetic nanoparticles for thermochemotherapy and magnetic resonance imaging of tumor

verfasst von: Fuping Gao, Zixing Yan, Jing Zhou, Yuanyuan Cai, Jintian Tang

Erschienen in: Journal of Nanoparticle Research | Ausgabe 10/2012

Einloggen

Aktivieren Sie unsere intelligente Suche, um passende Fachinhalte oder Patente zu finden.

search-config
loading …

Abstract

There is significant interest in recent years in developing magnetic nanoparticles (MNPs) having multifunctional characteristics with complimentary roles. In this study, methotrexate (MTX) was conjugated on the iron oxide magnetic nanoparticles surface via a poly(ethyleneimine) self-assembled monolayer (MTX–MNPs). The novel platform combined cancer chemotherapy, hyperthermia and potential monitoring of the progression of disease through magnetic resonance imaging (MRI). The conjugation of MTX on the magnetite surface was confirmed by Fourier transform infrared spectroscopy and change of zeta potential. Transmission electron microscope (TEM) showed that MTX–MNPs were morphologically spherical. The average diameter of MTX–MNPs was 30.1 ± 5.2 nm determined by dynamic light scattering. Magnetic measurements revealed that the saturation magnetization of MTX–MNPs reached 68.8 emu/g and the nanoparticles were superparamagnetic. The MTX–MNPs had good heating properties in an alternating magnetic field. TEM results showed that a larger number of MTX–MNPs were internalized into the MCF-7 cellular cytoplasm compared with the MNPs. The MTX–MNPs demonstrated highly synergistic antiproliferative effects of simultaneous chemotherapy and hyperthermia in MCF-7 breast cancer cells. A significant negative contrast enhancement was observed with magnetic resonance phantom imaging for MCF-7 cells over L929cells, when both were cultured with the nanoconjugate. The MTX–MNPs with combined characteristics of thermochemotherapy and MRI could be of high clinical significance in the treatment of tumor.

Sie haben noch keine Lizenz? Dann Informieren Sie sich jetzt über unsere Produkte:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

  • über 102.000 Bücher
  • über 537 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Finance + Banking
  • Management + Führung
  • Marketing + Vertrieb
  • Maschinenbau + Werkstoffe
  • Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

  • über 67.000 Bücher
  • über 390 Zeitschriften

aus folgenden Fachgebieten:

  • Automobil + Motoren
  • Bauwesen + Immobilien
  • Business IT + Informatik
  • Elektrotechnik + Elektronik
  • Energie + Nachhaltigkeit
  • Maschinenbau + Werkstoffe




 

Jetzt Wissensvorsprung sichern!

Literatur
Zurück zum Zitat Arruebo M, Fernández-Pacheco R, Ibarra MR, Santamaría J (2007) Magnetic nanoparticles for drug delivery. Nano Today 2:22–32CrossRef Arruebo M, Fernández-Pacheco R, Ibarra MR, Santamaría J (2007) Magnetic nanoparticles for drug delivery. Nano Today 2:22–32CrossRef
Zurück zum Zitat Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR (2002) Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta 1587:164–173CrossRef Banerjee D, Mayer-Kuckuk P, Capiaux G, Budak-Alpdogan T, Gorlick R, Bertino JR (2002) Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochim Biophys Acta 1587:164–173CrossRef
Zurück zum Zitat Brusentsov NA, Brusentsova TN, Filinova EY, Jurchenko NY, Kupriyanov DA, Pirogov YA, Dubina AI, Shumskikhd MN, Shumakov LI, Anashkina EN et al (2007) Magnetohydrodynamic thermochemotherapy and MRI of mouse tumors. J Magn Magn Mater 311:176–180CrossRef Brusentsov NA, Brusentsova TN, Filinova EY, Jurchenko NY, Kupriyanov DA, Pirogov YA, Dubina AI, Shumskikhd MN, Shumakov LI, Anashkina EN et al (2007) Magnetohydrodynamic thermochemotherapy and MRI of mouse tumors. J Magn Magn Mater 311:176–180CrossRef
Zurück zum Zitat Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499CrossRef Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499CrossRef
Zurück zum Zitat Corot C, Rober P, Idée J-M, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504CrossRef Corot C, Rober P, Idée J-M, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504CrossRef
Zurück zum Zitat Cronstein BN, Bertino JR (2000) Methotrexate. Birkhauser Verlag Basel, Switzerland, pp 9–49CrossRef Cronstein BN, Bertino JR (2000) Methotrexate. Birkhauser Verlag Basel, Switzerland, pp 9–49CrossRef
Zurück zum Zitat Dube D, Francis M, Leroux JC, Winnik FM (2002) Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate conjugates. Bioconjug Chem 13:685–692CrossRef Dube D, Francis M, Leroux JC, Winnik FM (2002) Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate conjugates. Bioconjug Chem 13:685–692CrossRef
Zurück zum Zitat Duthie SJ (2001) Folic-acid-mediated inhibition of human colon-cancer cell growth. Nutrition 17:736–737CrossRef Duthie SJ (2001) Folic-acid-mediated inhibition of human colon-cancer cell growth. Nutrition 17:736–737CrossRef
Zurück zum Zitat Gao J, Gu H, Xu B (2009) Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. Acc Chem Res 42:1097–1107CrossRef Gao J, Gu H, Xu B (2009) Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. Acc Chem Res 42:1097–1107CrossRef
Zurück zum Zitat Gao F, Cai Y, Zhou J, Xie X, Ouyang W, Zhang Y, Wang X, Zhang X, Wang X, Tang J et al (2010) Pullulan acetate coated magnetite nanoparticles for hyperthermia: preparation, characterization and in vitro experiments. Nano Res 3:23–31CrossRef Gao F, Cai Y, Zhou J, Xie X, Ouyang W, Zhang Y, Wang X, Zhang X, Wang X, Tang J et al (2010) Pullulan acetate coated magnetite nanoparticles for hyperthermia: preparation, characterization and in vitro experiments. Nano Res 3:23–31CrossRef
Zurück zum Zitat Gao F, Li L, Liu T, Hao N, Liu H, Tan L, Li H, Huang X, Peng B, Tang FQ et al (2012) Doxorubicin loaded silica nanorattle actively homing to tumor with improved anti-tumor effect. Nanoscale 4:3365–3372CrossRef Gao F, Li L, Liu T, Hao N, Liu H, Tan L, Li H, Huang X, Peng B, Tang FQ et al (2012) Doxorubicin loaded silica nanorattle actively homing to tumor with improved anti-tumor effect. Nanoscale 4:3365–3372CrossRef
Zurück zum Zitat Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499CrossRef Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, de la Rosette J, Weissleder R (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499CrossRef
Zurück zum Zitat Huh YM, Jun YW, Song HT, Kim S, Choi JS, Lee JH, Yoon S, Kim KS, Shin JS, Cheon J et al (2005) In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. J Am Chem Soc 127:12387–12391CrossRef Huh YM, Jun YW, Song HT, Kim S, Choi JS, Lee JH, Yoon S, Kim KS, Shin JS, Cheon J et al (2005) In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. J Am Chem Soc 127:12387–12391CrossRef
Zurück zum Zitat Islam T, Harisinghani MG (2009) Overview of nanoparticle use in cancer imaging. Cancer Biomark 5:61–67 Islam T, Harisinghani MG (2009) Overview of nanoparticle use in cancer imaging. Cancer Biomark 5:61–67
Zurück zum Zitat Ito A, Fujioka M, Yoshida T, Wakamatsu K, Ito S, Yamashita T, Jimbow K, Honda H (2007) 4-S-Cysteaminephenol-loaded magnetite cationic liposomes for combination therapy of hyperthermia with chemotherapy against malignant melanoma. Cancer Sci 98:424–430CrossRef Ito A, Fujioka M, Yoshida T, Wakamatsu K, Ito S, Yamashita T, Jimbow K, Honda H (2007) 4-S-Cysteaminephenol-loaded magnetite cationic liposomes for combination therapy of hyperthermia with chemotherapy against malignant melanoma. Cancer Sci 98:424–430CrossRef
Zurück zum Zitat Jain TK, Richey J, Strand M, Leslie-Pelecky DL, Flask CA, Labhasetwar V (2008) Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging. Biomaterials 29:4012–4021CrossRef Jain TK, Richey J, Strand M, Leslie-Pelecky DL, Flask CA, Labhasetwar V (2008) Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging. Biomaterials 29:4012–4021CrossRef
Zurück zum Zitat Jing Y, Moore LR, Williams PS, Chalmers JJ, Farag SS, Bolwell B, Zborowski M (2007) Blood progenitor cell separation from clinical leukapheresis product by magnetic nanoparticle binding and magnetophoresis. Biotechnol Bioeng 96:1139–1154CrossRef Jing Y, Moore LR, Williams PS, Chalmers JJ, Farag SS, Bolwell B, Zborowski M (2007) Blood progenitor cell separation from clinical leukapheresis product by magnetic nanoparticle binding and magnetophoresis. Biotechnol Bioeng 96:1139–1154CrossRef
Zurück zum Zitat Johannsen M, Thiesen B, Wust P, Jordan A (2010) Magnetic nanoparticle hyperthermia for prostate cancer. Int J Hyperth 26:790–795CrossRef Johannsen M, Thiesen B, Wust P, Jordan A (2010) Magnetic nanoparticle hyperthermia for prostate cancer. Int J Hyperth 26:790–795CrossRef
Zurück zum Zitat Kamruzzaman Selim KM, Ha YS, Kim SJ, Chang Y, Kim TJ, Lee GH, Kang IK (2007) Surface modification of magnetite nanoparticles using lactobionic acid and their interaction with hepatocytes. Biomaterials 28:710–716CrossRef Kamruzzaman Selim KM, Ha YS, Kim SJ, Chang Y, Kim TJ, Lee GH, Kang IK (2007) Surface modification of magnetite nanoparticles using lactobionic acid and their interaction with hepatocytes. Biomaterials 28:710–716CrossRef
Zurück zum Zitat Kohler N, Sun C, Fichtenholtz A, Gunn J, Fang C, Zhang M (2006) Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. Small 2:785–792CrossRef Kohler N, Sun C, Fichtenholtz A, Gunn J, Fang C, Zhang M (2006) Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. Small 2:785–792CrossRef
Zurück zum Zitat Li GY, Huang KL, Jiang YR, Ding P, Yang DL (2008) Preparation and characterization of carboxyl functionalization of chitosan derivative magnetic nanoparticles. Biochem Eng J 40:408–414CrossRef Li GY, Huang KL, Jiang YR, Ding P, Yang DL (2008) Preparation and characterization of carboxyl functionalization of chitosan derivative magnetic nanoparticles. Biochem Eng J 40:408–414CrossRef
Zurück zum Zitat McBain SC, Yiu HHP, Dobson J (2008) Magnetic nanoparticles for gene and drug delivery. Int J Nanomed 3:169–180 McBain SC, Yiu HHP, Dobson J (2008) Magnetic nanoparticles for gene and drug delivery. Int J Nanomed 3:169–180
Zurück zum Zitat Medarova Z, Pham W, Kim Y, Dai GP, Moore A (2006) In vivo imaging of tumor response to therapy using a dual-modality imaging strategy. Int J Cancer 118:2796–2802CrossRef Medarova Z, Pham W, Kim Y, Dai GP, Moore A (2006) In vivo imaging of tumor response to therapy using a dual-modality imaging strategy. Int J Cancer 118:2796–2802CrossRef
Zurück zum Zitat Mikhaylova M, Kim DK, Berry CC, Zagorodni A, Toprak M, Curtis ASG, Muhammed M (2004) BSA immobilization on amine-functionalized superparamagnetic iron oxide nanoparticles. Chem Mater 16:2344–2354CrossRef Mikhaylova M, Kim DK, Berry CC, Zagorodni A, Toprak M, Curtis ASG, Muhammed M (2004) BSA immobilization on amine-functionalized superparamagnetic iron oxide nanoparticles. Chem Mater 16:2344–2354CrossRef
Zurück zum Zitat Mohamed F, Marchettini P, Stuart OA, Urano M, Sugarbaker PH (2003) Thermal enhancement of new chemotherapeutic agents at moderate hyperthermia. Ann Surg Oncol 10:463–468CrossRef Mohamed F, Marchettini P, Stuart OA, Urano M, Sugarbaker PH (2003) Thermal enhancement of new chemotherapeutic agents at moderate hyperthermia. Ann Surg Oncol 10:463–468CrossRef
Zurück zum Zitat Morishige K, Kacher DF, Libby P, Josephson L, Ganz P, Weissleder R, Aikawa M (2010) High-resolution magnetic resonance imaging enhanced with superparamagnetic nanoparticles measures macrophage burden in atherosclerosis. Circulation 122:1707–1715CrossRef Morishige K, Kacher DF, Libby P, Josephson L, Ganz P, Weissleder R, Aikawa M (2010) High-resolution magnetic resonance imaging enhanced with superparamagnetic nanoparticles measures macrophage burden in atherosclerosis. Circulation 122:1707–1715CrossRef
Zurück zum Zitat Park JY, Daksha P, Lee GH, Woo S, Chang Y (2008) Highly water-dispersible PEG surface modified ultra small superparamagnetic iron oxide nanoparticles useful for target-specific biomedical applications. Nanotechnology 19:365603–365609CrossRef Park JY, Daksha P, Lee GH, Woo S, Chang Y (2008) Highly water-dispersible PEG surface modified ultra small superparamagnetic iron oxide nanoparticles useful for target-specific biomedical applications. Nanotechnology 19:365603–365609CrossRef
Zurück zum Zitat Pradhan P, Giri J, Rieken F, Koch C, Mykhaylyk O, Döblinger M, Banerjee R, Bahadur D, Plank C (2010) Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Control Release 142:108–121CrossRef Pradhan P, Giri J, Rieken F, Koch C, Mykhaylyk O, Döblinger M, Banerjee R, Bahadur D, Plank C (2010) Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Control Release 142:108–121CrossRef
Zurück zum Zitat Purushotham S, Ramanujan RV (2010) Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy. Acta Biomater 6:502–510CrossRef Purushotham S, Ramanujan RV (2010) Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy. Acta Biomater 6:502–510CrossRef
Zurück zum Zitat Riehemann K, Schmitt O, Ehlers EM (2005) The effects of thermochemotherapy using cyclophosphamide plus hyperthermia on the malignant pleural mesothelioma in vivo. Ann Anat 187:215–223CrossRef Riehemann K, Schmitt O, Ehlers EM (2005) The effects of thermochemotherapy using cyclophosphamide plus hyperthermia on the malignant pleural mesothelioma in vivo. Ann Anat 187:215–223CrossRef
Zurück zum Zitat Sanson C, Diou O, Thevenot J, Ibarboure E, Soum A, Brulet A, Miraux S, Thiaudiere E, Tan S, Brisson A, Dupuis V, Sandre O, Lecommandoux S (2011) Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy. ACS Nano 5:1122–1140CrossRef Sanson C, Diou O, Thevenot J, Ibarboure E, Soum A, Brulet A, Miraux S, Thiaudiere E, Tan S, Brisson A, Dupuis V, Sandre O, Lecommandoux S (2011) Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy. ACS Nano 5:1122–1140CrossRef
Zurück zum Zitat Seo SB, Yang J, Hyung W, Cho EJ, Lee TI, Song YJ, Yoon HG, Suh JS, Huh YM, Haam S (2007) Novel multifunctional PHDCA/PEI nano-drug carriers for simultaneous magnetically targeted cancer therapy and diagnosis via magnetic resonance imaging. Nanotechnology 18:475105CrossRef Seo SB, Yang J, Hyung W, Cho EJ, Lee TI, Song YJ, Yoon HG, Suh JS, Huh YM, Haam S (2007) Novel multifunctional PHDCA/PEI nano-drug carriers for simultaneous magnetically targeted cancer therapy and diagnosis via magnetic resonance imaging. Nanotechnology 18:475105CrossRef
Zurück zum Zitat Sudimack J, Lee RJ (2000) Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev 41:147–162CrossRef Sudimack J, Lee RJ (2000) Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev 41:147–162CrossRef
Zurück zum Zitat Sun C, Sze R, Zhang M (2006) Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. J Biomed Mater Res A 78:550–557 Sun C, Sze R, Zhang M (2006) Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. J Biomed Mater Res A 78:550–557
Zurück zum Zitat Takemoto M, Kuroda M, Urano M, Nishimura Y, Kawasaki S, Kato H, Okumura Y, Akaki S, Kanazawa S, Hiraki Y et al (2003) The effect of various chemotherapeutic agents given with mild hyperthermia on different types of tumours. Int J Hyperth 19:193–203CrossRef Takemoto M, Kuroda M, Urano M, Nishimura Y, Kawasaki S, Kato H, Okumura Y, Akaki S, Kanazawa S, Hiraki Y et al (2003) The effect of various chemotherapeutic agents given with mild hyperthermia on different types of tumours. Int J Hyperth 19:193–203CrossRef
Zurück zum Zitat Thiesen B, Jordan A (2008) Clinical applications of magnetic nanoparticles for hyperthermia. Int J Hyperth 24:467–474CrossRef Thiesen B, Jordan A (2008) Clinical applications of magnetic nanoparticles for hyperthermia. Int J Hyperth 24:467–474CrossRef
Zurück zum Zitat Trippett TM, Garcia S, Manova K, Mody R, Cohen-Gould FlintoffW, Bertino JR (2001) Localization of a human reduced folate carrier protein in the mitochondrial as well as the cell membrane of leukemia cells. Cancer Res 61:1941–1947 Trippett TM, Garcia S, Manova K, Mody R, Cohen-Gould FlintoffW, Bertino JR (2001) Localization of a human reduced folate carrier protein in the mitochondrial as well as the cell membrane of leukemia cells. Cancer Res 61:1941–1947
Zurück zum Zitat Wang X, Zhou L, Ma Y, Li X, Gu H (2009) Control of aggregate size of polyethyleneimine-coated magnetic nanoparticles for magnetofection. Nano Res 2:365–372CrossRef Wang X, Zhou L, Ma Y, Li X, Gu H (2009) Control of aggregate size of polyethyleneimine-coated magnetic nanoparticles for magnetofection. Nano Res 2:365–372CrossRef
Zurück zum Zitat Wang L, Neoh KG, Kang ET, Shuter B, Wang SC (2010) Biodegradable magnetic-fluorescent magnetite/poly(dl-lactic acid-co-α, β-malic acid) composite nanoparticles for stem cell labeling. Biomaterials 31:3502–3511CrossRef Wang L, Neoh KG, Kang ET, Shuter B, Wang SC (2010) Biodegradable magnetic-fluorescent magnetite/poly(dl-lactic acid-co-α, β-malic acid) composite nanoparticles for stem cell labeling. Biomaterials 31:3502–3511CrossRef
Zurück zum Zitat Weissleder R, Kelly K, Sun EY, Shtatland T, Josephson L (2005) Cell specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 23:1418–1423CrossRef Weissleder R, Kelly K, Sun EY, Shtatland T, Josephson L (2005) Cell specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 23:1418–1423CrossRef
Zurück zum Zitat Yallapu MM, Othman SF, Curtis ET, Gupta BK, Jaggi M, Chauhan SC (2011) Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy. Biomaterials 32:1890–1905CrossRef Yallapu MM, Othman SF, Curtis ET, Gupta BK, Jaggi M, Chauhan SC (2011) Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy. Biomaterials 32:1890–1905CrossRef
Zurück zum Zitat Yan G-P, Robinson L, Hogg P (2007) Magnetic resonance imaging contrast agents: overview and perspectives. Radiography 13:e5–e19CrossRef Yan G-P, Robinson L, Hogg P (2007) Magnetic resonance imaging contrast agents: overview and perspectives. Radiography 13:e5–e19CrossRef
Metadaten
Titel
Methotrexate-conjugated magnetic nanoparticles for thermochemotherapy and magnetic resonance imaging of tumor
verfasst von
Fuping Gao
Zixing Yan
Jing Zhou
Yuanyuan Cai
Jintian Tang
Publikationsdatum
01.10.2012
Verlag
Springer Netherlands
Erschienen in
Journal of Nanoparticle Research / Ausgabe 10/2012
Print ISSN: 1388-0764
Elektronische ISSN: 1572-896X
DOI
https://doi.org/10.1007/s11051-012-1160-6

Weitere Artikel der Ausgabe 10/2012

Journal of Nanoparticle Research 10/2012 Zur Ausgabe

    Marktübersichten

    Die im Laufe eines Jahres in der „adhäsion“ veröffentlichten Marktübersichten helfen Anwendern verschiedenster Branchen, sich einen gezielten Überblick über Lieferantenangebote zu verschaffen.