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Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles

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Abstract

Stable 30–50 nm polymeric polyethylene glycol–phosphatidylethanolamine (PEG–PE)-based micelles entrapping superparamagnetic iron oxide nanoparticles (SPION) have been prepared. At similar concentrations of SPION, the SPION-micelles had significantly better magnetic resonance imaging (MRI) T2 relaxation signal compared to ‘plain’ SPION. Freeze-fracture electron microscopy confirmed SPION entrapment in the lipid core of the PEG–PE micelles. To enhance the targeting capability of these micelles, their surface was modified with the cancer cell-specific anti-nucleosome monoclonal antibody 2C5 (mAb 2C5). Such mAb 2C5-SPION immunomicelles demonstrated specific binding with cancer cells in vitro and were able to bring more SPION to the cancer cells thus demonstrating the potential to be used as targeted MRI contrast agents for tumor imaging.

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References

  • Ai H, Flask C, Weinberg B, Shuai X, Pagel MD, Farell D, Duerk J, Gao J (2005) Magnetite-loaded polymeric micelles as novel magnetic resonance probes. Adv Mater 26:3995–4021

    Google Scholar 

  • Alexiou C, Jurgons R, Schmid RJ, Bergemann C, Henke J, Erhardt W, Huenges E, Parak F (2003) Magnetic drug targeting-biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment. J Drug Target 11:139–149. doi:10.1080/1061186031000150791

    Article  PubMed  CAS  Google Scholar 

  • Corot C, Robert P, Idee JM, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504. doi:10.1016/j.addr.2006.09.013

    Article  PubMed  CAS  Google Scholar 

  • Dandamudi S, Campbell RB (2007) Development and characterization of magnetic cationic liposomes for targeting tumor microvasculature. Biochim Biophys Acta 1768:427–438. doi:10.1016/j.bbamem.2006.10.006

    Article  PubMed  CAS  Google Scholar 

  • Durand E, Raynaud JS, Bruneval P, Brigger I, Al Haj Zen A, Mandet C, Lancelot E, Lafont A (2007) Magnetic resonance imaging of ruptured plaques in the rabbit with ultrasmall superparamagnetic particles of iron oxide. J Vasc Res 44:119–128. doi:10.1159/000098484

    Article  PubMed  CAS  Google Scholar 

  • Elbayoumi TA, Torchilin VP (2007) Enhanced cytotoxicity of monoclonal anticancer antibody 2C5-modified doxorubicin-loaded PEGylated liposomes against various tumor cell lines. Eur J Pharm Sci 32:159–168. doi:10.1016/j.ejps.2007.05.113

    Article  PubMed  CAS  Google Scholar 

  • Elbayoumi TA, Torchilin VP (2008) Tumor-specific antibody-mediated targeted delivery of Doxil® reduces the manifestation of auricular erythema side effect in mice. Int J Pharm 357:272–279. doi:10.1016/j.ijpharm.2008.01.041

    Article  PubMed  CAS  Google Scholar 

  • Elbayoumi TA, Pabba S, Roby A, Torchilin VP (2007) Antinucleosome antibody-modified liposomes and lipid-core micelles for tumor-targeted delivery of therapeutic and diagnostic agents. J Liposome Res 17:1–14. doi:10.1080/08982100601186474

    Article  PubMed  CAS  Google Scholar 

  • Erdogan S, Medarova ZO, Roby A, Moore A, Torchilin VP (2008) Enhanced tumor MR imaging with gadolinium-loaded polychelating polymer-containing tumor-targeted liposomes. J Magn Reson Imaging 27:574–580. doi:10.1002/jmri.21202

    Article  PubMed  Google Scholar 

  • Fortin JP, Wilhelm C, Servais J, Menager C, Bacri JC, Gazeau F (2007) Size-sorted anionic iron oxide nanomagnets as colloidal mediators for magnetic hyperthermia. J Am Chem Soc 129:2628–2635. doi:10.1021/ja067457e

    Article  PubMed  CAS  Google Scholar 

  • Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021. doi:10.1016/j.biomaterials.2004.10.012

    Article  PubMed  CAS  Google Scholar 

  • Gupta B, Levchenko TS, Mongayt DA, Torchilin VP (2005) Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo. J Drug Target 13:337–343. doi:10.1080/10611860500286239

    Article  PubMed  CAS  Google Scholar 

  • Hyeon T, Lee SS, Park J, Chung Y, Na HB (2001) Synthesis of highly crystalline and monodisperse maghemite nanocrystallites without a size-selection process. J Am Chem Soc 123:12798–12801. doi:10.1021/ja016812s

    Article  PubMed  CAS  Google Scholar 

  • Iakoubov LZ, Torchilin VP (1997) A novel class of antitumor antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice. Oncol Res 9:439–446

    PubMed  CAS  Google Scholar 

  • Iakoubov LZ, Torchilin VP (1998) Nucleosome-releasing treatment makes surviving tumor cells better targets for nucleosome-specific anticancer antibodies. Cancer Detect Prev 22:470–475. doi:10.1046/j.1525-1500.1998.00055.x

    Article  PubMed  CAS  Google Scholar 

  • Iakoubov L, Rokhlin O, Torchilin V (1995) Anti-nuclear autoantibodies of the aged reactive against the surface of tumor but not normal cells. Immunol Lett 47:147–149. doi:10.1016/0165-2478(95)00066-E

    Article  PubMed  CAS  Google Scholar 

  • Ito A, Shinkai M, Honda H, Kobayashi T (2005) Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng 100:1–11. doi:10.1263/jbb.100.1

    Article  PubMed  CAS  Google Scholar 

  • Ito A, Honda H, Kobayashi T (2006) Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of “heat-controlled necrosis” with heat shock protein expression. Cancer Immunol Immunother 55:320–328. doi:10.1007/s00262-005-0049-y

    Article  PubMed  CAS  Google Scholar 

  • Jin H, Hong B, Kakar SS, Kang KA (2008) Tumor-specific nano-entities for optical detection and hyperthermic treatment of breast cancer. Adv Exp Med Biol 614:275–284. doi:10.1007/978-0-387-74911-2_31

    Article  PubMed  Google Scholar 

  • Johannsen M, Thiesen B, Gneveckow U, Taymoorian K, Waldofner N, Scholz R, Deger S, Jung K, Loening SA, Jordan A (2006) Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer. Prostate 66:97–104. doi:10.1002/pros.20324

    Article  PubMed  CAS  Google Scholar 

  • Kang HW, Josephson L, Petrovsky A, Weissleder R, Bogdanov A Jr (2002) Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjug Chem 13:122–127. doi:10.1021/bc0155521

    Article  PubMed  CAS  Google Scholar 

  • Kubo T, Sugita T, Shimose S, Nitta Y, Ikuta Y, Murakami T (2001) Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters. Int J Oncol 18:121–125

    PubMed  CAS  Google Scholar 

  • Lukyanov AN, Elbayoumi TA, Chakilam AR, Torchilin VP (2004) Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. J Control Release 100:135–144. doi:10.1016/j.jconrel.2004.08.007

    Article  PubMed  CAS  Google Scholar 

  • Martina MS, Fortin JP, Fournier L, Menager C, Gazeau F, Clement O, Lesieur S (2007) Magnetic targeting of rhodamine-labeled superparamagnetic liposomes to solid tumors: in vivo tracking by fibered confocal fluorescence microscopy. Mol Imaging 6:140–146

    PubMed  CAS  Google Scholar 

  • Mathieu JB, Martel S (2007) Magnetic microparticle steering within the constraints of an MRI system: proof of concept of a novel targeting approach. Biomed Microdevices 9:801–808. doi:10.1007/s10544-007-9092-0

    Article  PubMed  Google Scholar 

  • Mulder WJ, Griffioen AW, Strijkers GJ, Cormode DP, Nicolay K, Fayad ZA (2007) Magnetic and fluorescent nanoparticles for multimodality imaging. Nanomedicine 2:307–324. doi:10.2217/17435889.2.3.307

    Article  PubMed  CAS  Google Scholar 

  • Munshi N, De TK, Maitra A (1997) Size modulation of polymeric nanoparticles under controlled dynamics of microemulsion droplets. J Colloid Interface Sci 190:387–391. doi:10.1006/jcis.1997.4889

    Article  PubMed  Google Scholar 

  • Nasongkla N, Bey E, Ren J, Ai H, Khemtong C, Guthi JS, Chin SF, Sherry AD, Boothman DA, Gao J (2006) Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6:2427–2430. doi:10.1021/nl061412u

    Article  PubMed  ADS  CAS  Google Scholar 

  • Sawant RR, Sawant RM, Torchilin VP (2008) Mixed PEG–PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: improved drug solubilization and enhanced in vitro cytotoxicity. Eur J Pharm Biopharm 70:51–57. doi:10.1016/j.ejpb.2008.04.016

    Article  PubMed  CAS  Google Scholar 

  • Silva AK, Silva EL, Carrico AS, Egito ES (2007) Magnetic carriers: a promising device for targeting drugs into the human body. Curr Pharm Des 13:1179–1185. doi:10.2174/138161207780618993

    Article  PubMed  CAS  Google Scholar 

  • Sun C, Veiseh O, Gunn J, Fang C, Hansen S, Lee D, Sze R, Ellenbogen RG, Olson J, Zhang M (2008) In vivo MRI detection of gliomas by chlorotoxin-conjugated superparamagnetic nanoprobes. Small 4:372–379. doi:10.1002/smll.200700784

    Article  PubMed  CAS  Google Scholar 

  • Sykova E, Jendelova P (2007) In vivo tracking of stem cells in brain and spinal cord injury. Prog Brain Res 161:367–383. doi:10.1016/S0079-6123(06)61026-1

    Article  PubMed  CAS  Google Scholar 

  • Tang T, Zheng JW, Chen B, Li H, Li X, Xue KY, Ai X, Zou SQ (2007) Effects of targeting magnetic drug nanoparticles on human cholangiocarcinoma xenografts in nude mice. Hepatobiliary Pancreat Dis Int 6:303–307

    PubMed  CAS  Google Scholar 

  • Torchilin VP (2004) Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol Life Sci 61:2549–2559. doi:10.1007/s00018-004-4153-5

    Article  PubMed  CAS  Google Scholar 

  • Torchilin VP, Levchenko TS, Lukyanov AN, Khaw BA, Klibanov AL, Rammohan R, Samokhin GP, Whiteman KR (2001) p-Nitrophenylcarbonyl-PEG–PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. Biochim Biophys Acta 1511:397–411. doi:10.1016/S0005-2728(01)00165-7

    Article  PubMed  CAS  Google Scholar 

  • Torchilin VP, Lukyanov AN, Gao Z, Papahadjopoulos-Sternberg B (2003) Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad Sci USA 100:6039–6044. doi:10.1073/pnas.0931428100

    Article  PubMed  ADS  CAS  Google Scholar 

  • Wada S, Tazawa K, Furuta I, Nagae H (2003) Antitumor effect of new local hyperthermia using dextran magnetite complex in hamster tongue carcinoma. Oral Dis 9:218–223. doi:10.1034/j.1601-0825.2003.02839.x

    Article  PubMed  CAS  Google Scholar 

  • Yang F, de Fu L, Long J, Ni QX (2008) Magnetic lymphatic targeting drug delivery system using carbon nanotubes. Med Hypotheses 70:765–767. doi:10.1016/j.mehy.2007.07.045

    Article  PubMed  CAS  Google Scholar 

  • Zhang C, Jugold M, Woenne EC, Lammers T, Morgenstern B, Mueller MM, Zentgraf H, Bock M, Eisenhut M, Semmler W, Kiessling F (2007) Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Res 67:1555–1562. doi:10.1158/0008-5472.CAN-06-1668

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported by the NIH grants RO1 EB01961 and RO1 EN002995 to Vladimir P. Torchilin and by Northeastern University and NSF grant DGE-0504331 to Srinivas Sridhar.

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Correspondence to Vladimir P. Torchilin.

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Sawant, R.M., Sawant, R.R., Gultepe, E. et al. Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles. J Nanopart Res 11, 1777–1785 (2009). https://doi.org/10.1007/s11051-009-9611-4

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