شماره 46 - بهار 1396
ICNS7
شماره 47-تابستان 1396
فهرست

مطالعه مروری بر انواع نانو سامانه های هدفمند مغناطیسی حامل داروی دوکسوروبیسن و تاثیر آن ها بر مرگ سلول های سرطانی

نشریه: شماره 46-بهار 1396 - مقاله 2   صفحات :  9 تا 20



کد مقاله:
46-02

مولفین:
محمد قنبری


چکیده مقاله:

سرطان یکی از بیماری¬های مهلکی است که هنوز بشر علارقم پیشرفت¬های زیاد قادر به کنترل آن نشده است. دوکسوروبیسن یکی از داروهای مرسومی است که در شیمی درمانی سرطان استفاده می شود و به دلیل تاثیر سیستمیک و سمیت بالا بر بافت های سالم بدن کاربرد آن با محدودیت روبروست. فناوری نانو با تولید نانو ذرات هدفمند مغناطیسی جهت رسانش مستقیم این دارو به سلول های سرطانی بسیاری از محدودیت ها و اثرات جانبی استفاده از آن را برداشته است. امروزه انواع نانو سامانه های هوشمند مغناطیسی بر اساس نانو ذرات اکسید آهن که انتقال هدفمند دوکسوروبیسین به بافت تومور را میسر می سازند توسعه پیدا کرده اند و قابلیت هدفمند سازی هر یک از این سامانه های دارویی توسط لیگاندهای هدفمند مولکولی مختص سلول های سرطانی و نیز بکارگیری میدان مغناطیسی خارجی جهت متمرکز کردن این نانو سامانه های مغناطیسی در مکان تومور فراهم شده است. مقاله حاضر پتانسیل نانوذرات اکسیدآهن را در طراحی نانوحامل¬های مغناطیسی جدید و هدفمند، برای انتقال و تقویت سمیت داروی دوکسوروبیسن به سلول های سرطانی را شرح می دهد


Article's English abstract:

Cancer is a deadly disease that human have not been able to control it, Despite of much breakthroughs. Doxorubicin is one of the conventional drugs used in cancer chemotherapy and because of systemic effects and high toxicity on healthy tissues of the body, its application is faced with restrictions. Nanotechnology with development of targeted magnetic nanoparticles to deliver of Doxorubicin directly to cancer cells, has removed a lot of restrictions and its side effects. Today, a variety of intelligent nano-systems based on magnetic iron oxide nanoparticles that allow the targeted delivery of doxorubicin to tumor tissues, have been developed, and the possibility of targeting the each of these pharmaceutical systems by molecular targeted cancer cell-specific ligands and using an external magnetic field to concentrate the magnetic nano-systems in tumor location is provided. This article explains the potential of iron oxide nanoparticles in the design of new and targeted magnetic carriers to augment the toxic effects and delivery of doxorubicin to tumor cells


کلید واژگان:
دارو رسانی، دوکسوروبیسن، سرطان، نانو ذرات اکسید آهن

English Keywords:
Cancer, Doxorubicin, Iron oxide nanoparticles, Drug delivery

منابع:
1. Xing M, Yan F, Yu S and Shen P. Efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy in advanced breast cancer: a meta-analysis of ten randomized controlled trials. PloS one, 10(7): e0133569, 2015. 2. Kibria G, Hatakeyama H, Sato Y and Harashima H. Anti-Tumor Effect via Passive Anti-angiogenesis of PEGylated Liposomes Encapsulating Doxorubicin in Drug Resistant Tumors. International journal of pharmaceutics, 2016. 3. Leonard R.C, Williams S, Tulpule A, Levine A.M, Oliveros S. Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet). Breast, 18: 218-224, 2009. 4. Lühmann T, Meinel L. Nanotransporters for drug delivery. Current opinion in biotechnology, 39: 35-40, 2016. 5. Shevtsov M.A, Multhoff G. Recent developments of magnetic nanoparticles for theranostics of brain tumor. Current drug metabolism, 2016. 6. Cole A.J, Yang V.C, David A.E. Cancer theranostics: the rise of targeted magnetic nanoparticles. Trends in biotechnology. 29: 323-332, 2011. 7. Ghanbari M, Asadi A, Rostamzadeh S. Study of the Cytotoxicity Effect of Doxorubicin-loaded/Folic acid-Targeted Super Paramagnetic Iron Oxide Nanoparticles on AGS Cancer Cell Line. J Nanomed Nanotechnol, 7(368):2, 2016. 8. Hajba L, Guttman A. The use of magnetic nanoparticles in cancer theranostics: Toward handheld diagnostic devices. Biotechnology advances, 34(4): 354-361, 2016. 9. Masoudi A, Madaah Hosseini H.R, Seyed Reyhani S.M, Shokrgozar M.A, Oghabian M.A, Ahmadi R. Long-term investigation on the phase stability, magnetic behavior, toxicity, and MRI characteristics of superparamagnetic Fe/Fe-oxide core/shell nanoparticles. International Journal of Pharmaceutics. 439: 28-40, 2012. 10. McBain S.C, Yiu H.H, Dobson J. Magnetic nanoparticles for gene and drug delivery. International Journal of Nanomedicine. 3: 169-180, 2008. 11. Heidari Majd M, Asgari D, Barar J, Valizadeh H, Kafil V, Abadpour A, Moumivand E, Mojarrad J.S, Rashidi M.R, Coukos G, Omidi, Y. Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imagingand therapy of cancer. Colloids and Surfaces B: Biointerfaces. 106: 117-125, 2013. 12. Cohen Y, Shoushan S.Y. Magnetic nanoparticles-based diagnostics and theranostics. Current Opinion in Biotechnology. 24: 672-681, 2013. 13. Galluzzi L, Kroemer G. A four-lane highway to cancer. Nature Reviews Molecular Cell Biology, 2016. 14. Jain T.K, Richey J, Strand M, Leslie-Pelecky D.L, Flask C.A, Labhasetwar V. Magnetic nanoparticles with dual functional properties: Drug delivery and magnetic resonance imaging. Biomaterials. 29: 4012-4021, 2008. 15. Zuccala E. Chemotherapy: Clocking up resistance. Nature Reviews Cancer, 2016. 16. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. Journal of Controlled Release, 200:138-157, 2015. 17. Xu R, Zhang G, Mai J, Deng X, Segura-Ibarra V, Wu S, Shen J, Liu H, Hu Z, Chen L and Huang Y. An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nature biotechnology, 2016. 18. Benyettou F, Flores O, Alonso J, Ravaux F, Rezgui R, Jouiad M, Nehme SI, Parsapur RK, Olsen JC, Selvam P, Trabolsi A. Mesoporous γ-Iron Oxide Nanoparticles for Magnetically Triggered Release of Doxorubicin and Hyperthermia Treatment. Chemistry-A European Journal. 14;22(47):17020-8, 2016. 19. Mosafer J, Abnous K, Tafaghodi M, Mokhtarzadeh A, Ramezani M. In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy. European Journal of Pharmaceutics and Biopharmaceutics. 30;113:60-74, 2017. 20. Gupta A.K, Wells S. Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE transactions on nanobioscience. 3: 66-73, 2004. 21. Aljarrah K, Mhaidat N.M, Al-Akhras M.A, Aldaher A.N, Albiss B, Aledealat K, Alsheyab F.M. Magnetic nanoparticles sensitize MCF-7 breast cancer cells to doxorubicin-induced apoptosis. World Journal of Surgical Oncology. 10: 62, 2012. 22. Gonzales M, Mitsumori L.M, Kushleika J.V, Rosenfeld M.E, Krishnan K.M. Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127. Contrast Media and Molecular Imaging. 5: 286-293, 2010. 23. Yang X, Chen L, Han B, Yang X, Duan H. Preparation of magnetite and tumor dual-targeting hollow polymer microspheres with pH-sensitivity for anticancer drug-carriers. Polymer. 51: 2533-2539, 2010. 24. Munnier E, Cohen-Jonathan S, Linassier C, Douziech-Eyrolles L, Marchais H, Souce M, Herve K, Dubois P, Chourpa I. Novel method of doxorubicin-SPION reversible association for magnetic drug targeting. International Journal of Pharmaceutics. 363: 170-176, 2008. 25. Munnier E, Cohen-Jonathan S, Herve´ K, Linassier C, Souce´ M, Dubois P, Chourpa I. Doxorubicin delivered to MCF-7 cancer cellsby superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity. Journal of Nanoparticle Research. 13: 959-971, 2011. 26. Naqvi S, Samim M, Abdin M, Ahmed F.J, Maitra A, Prashant C, Dinda A.K. Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress. International Journal of Nanomedicine. 5: 983-989, 2010. 27. Kayal S, Ramanujan R.V. Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery. Materials Science and Engineering: C. 30: 484-490, 2010. 28. Shen F, Chu S, Bence A.K, Bailey B, Xue X, Erickson P.A. Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Journal of Pharmacology and Experimental Therapeutics. 324:95-102, 2008. 29. Shen Y, Tang H, Zhan Y, Van Kirk E.A, Murdoch W.J. Degradable Poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine : nanotechnology, biology, and medicine. 5: 192-201, 2009. 30. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecularadvances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews. 56: 185-229, 2004. 31. Mhaidat N.M, Alali F.Q, Matalqah S.M, Matalka II, Jaradat S.A, Al-Sawalha N.A, Thorne R.F. Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78. Anticancer Drugs. 20: 601-606, 2009. 32. Larochelle S. Oxidative damage: A pathway to stress. Nature chemical biology, 12(2), pp.53-53, 2016. 33. Apopa P.L, Qian Y, Shao R, Guo N.L, Schwegler-Berry D, Pacurari M, Porter D, Shi X, Vallyathan V, Castranova V, Flynn D.C. Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Particle and Fibre Toxicology. 6: 1, 2009. 34. Ahamed M, Akhtar M.J, Khan M.M, Alhadlaq H.A and Alshamsan A. Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2). Colloids and Surfaces B: Biointerfaces, 148: 665-673, 2016. 35. Choi S.J, Oh J.M, Choy J.H. Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. Journal of Inorganic Biochemistry. 103: 463-471, 2009. 36. Aroui S, Brahim S, De Waard M, Breard J, Kenani A. Efficient induction of apoptosis by doxorubicin coupled to cell-penetrating peptides compared to unconjugated doxorubicin in the human breast cancer cell line MDA-MB 231. Cancer Letters. 285: 28-38, 2009a. 37. Netto C, Toma H.E, Andrade L.H. Superparamagnetic nanoparticles as versatile carriers and supporting materials for enzymes. Journal of Molecular Catalysis B: Enzymatic. 86: 71-92, 2012. 38. Yang Y, Guo Q, Peng J, Su J, Lu X, Zhao Y and Qian Z. Doxorubicin-Conjugated Heparin-Coated Superparamagnetic Iron Oxide Nanoparticles for Combined Anticancer Drug Delivery and Magnetic Resonance Imaging. Journal of Biomedical Nanotechnology, 12(11): 1963-1974, 2016. 39. Mallick N, Anwar M, Asfer M, Mehdi S.H, Rizvi M.M.A, Panda A.K, Talegaonkar S and Ahmad F.J. Chondroitin sulfate-capped super-paramagnetic iron oxide nanoparticles as potential carriers of doxorubicin hydrochloride. Carbohydrate Polymers, 2016. 40. Wei H, Bruns O.T, Chen O and Bawendi M.G. NANOPARTICLES FOR MAGNETIC RESONANCE IMAGING APPLICATIONS. Massachusetts Institute of Technology, U.S. Patent 20,160,074,538, 2016. 41. Xu C, Sun S. New forms of superparamagnetic nanoparticles for biomedical applications. Advanced Drug Delivery Reviews. 65: 732-743, 2012. 42. Mahmoudi M, Simchi A, Imani M, Shokrgozar M.A, Milani A.S, Hafeli U.O, Stroeve P .A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles.Colloids and Surfaces B: Biointerfaces. 75: 300-309, 2010. 43. Kearney A.S. Prodrugs and targeted drug delivery. Advanced Drug Delivery Reviews. 19: 225-239, 1996. 44. Gautier J, Allard-Vannier E, Munnier E, Souc M, Chourpa I. Recent advances in theranostic nanocarriers of doxorubicin based on iron oxide and gold nanoparticles. Journal of Controlled Release. 169: 48-61, 2013.

English References:
1. Xing M, Yan F, Yu S and Shen P. Efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy in advanced breast cancer: a meta-analysis of ten randomized controlled trials. PloS one, 10(7): e0133569, 2015. 2. Kibria G, Hatakeyama H, Sato Y and Harashima H. Anti-Tumor Effect via Passive Anti-angiogenesis of PEGylated Liposomes Encapsulating Doxorubicin in Drug Resistant Tumors. International journal of pharmaceutics, 2016. 3. Leonard R.C, Williams S, Tulpule A, Levine A.M, Oliveros S. Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet). Breast, 18: 218-224, 2009. 4. Lühmann T, Meinel L. Nanotransporters for drug delivery. Current opinion in biotechnology, 39: 35-40, 2016. 5. Shevtsov M.A, Multhoff G. Recent developments of magnetic nanoparticles for theranostics of brain tumor. Current drug metabolism, 2016. 6. Cole A.J, Yang V.C, David A.E. Cancer theranostics: the rise of targeted magnetic nanoparticles. Trends in biotechnology. 29: 323-332, 2011. 7. Ghanbari M, Asadi A, Rostamzadeh S. Study of the Cytotoxicity Effect of Doxorubicin-loaded/Folic acid-Targeted Super Paramagnetic Iron Oxide Nanoparticles on AGS Cancer Cell Line. J Nanomed Nanotechnol, 7(368):2, 2016. 8. Hajba L, Guttman A. The use of magnetic nanoparticles in cancer theranostics: Toward handheld diagnostic devices. Biotechnology advances, 34(4): 354-361, 2016. 9. Masoudi A, Madaah Hosseini H.R, Seyed Reyhani S.M, Shokrgozar M.A, Oghabian M.A, Ahmadi R. Long-term investigation on the phase stability, magnetic behavior, toxicity, and MRI characteristics of superparamagnetic Fe/Fe-oxide core/shell nanoparticles. International Journal of Pharmaceutics. 439: 28-40, 2012. 10. McBain S.C, Yiu H.H, Dobson J. Magnetic nanoparticles for gene and drug delivery. International Journal of Nanomedicine. 3: 169-180, 2008. 11. Heidari Majd M, Asgari D, Barar J, Valizadeh H, Kafil V, Abadpour A, Moumivand E, Mojarrad J.S, Rashidi M.R, Coukos G, Omidi, Y. Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imagingand therapy of cancer. Colloids and Surfaces B: Biointerfaces. 106: 117-125, 2013. 12. Cohen Y, Shoushan S.Y. Magnetic nanoparticles-based diagnostics and theranostics. Current Opinion in Biotechnology. 24: 672-681, 2013. 13. Galluzzi L, Kroemer G. A four-lane highway to cancer. Nature Reviews Molecular Cell Biology, 2016. 14. Jain T.K, Richey J, Strand M, Leslie-Pelecky D.L, Flask C.A, Labhasetwar V. Magnetic nanoparticles with dual functional properties: Drug delivery and magnetic resonance imaging. Biomaterials. 29: 4012-4021, 2008. 15. Zuccala E. Chemotherapy: Clocking up resistance. Nature Reviews Cancer, 2016. 16. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. Journal of Controlled Release, 200:138-157, 2015. 17. Xu R, Zhang G, Mai J, Deng X, Segura-Ibarra V, Wu S, Shen J, Liu H, Hu Z, Chen L and Huang Y. An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nature biotechnology, 2016. 18. Benyettou F, Flores O, Alonso J, Ravaux F, Rezgui R, Jouiad M, Nehme SI, Parsapur RK, Olsen JC, Selvam P, Trabolsi A. Mesoporous ?-Iron Oxide Nanoparticles for Magnetically Triggered Release of Doxorubicin and Hyperthermia Treatment. Chemistry-A European Journal. 14;22(47):17020-8, 2016. 19. Mosafer J, Abnous K, Tafaghodi M, Mokhtarzadeh A, Ramezani M. In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy. European Journal of Pharmaceutics and Biopharmaceutics. 30;113:60-74, 2017. 20. Gupta A.K, Wells S. Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE transactions on nanobioscience. 3: 66-73, 2004. 21. Aljarrah K, Mhaidat N.M, Al-Akhras M.A, Aldaher A.N, Albiss B, Aledealat K, Alsheyab F.M. Magnetic nanoparticles sensitize MCF-7 breast cancer cells to doxorubicin-induced apoptosis. World Journal of Surgical Oncology. 10: 62, 2012. 22. Gonzales M, Mitsumori L.M, Kushleika J.V, Rosenfeld M.E, Krishnan K.M. Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127. Contrast Media and Molecular Imaging. 5: 286-293, 2010. 23. Yang X, Chen L, Han B, Yang X, Duan H. Preparation of magnetite and tumor dual-targeting hollow polymer microspheres with pH-sensitivity for anticancer drug-carriers. Polymer. 51: 2533-2539, 2010. 24. Munnier E, Cohen-Jonathan S, Linassier C, Douziech-Eyrolles L, Marchais H, Souce M, Herve K, Dubois P, Chourpa I. Novel method of doxorubicin-SPION reversible association for magnetic drug targeting. International Journal of Pharmaceutics. 363: 170-176, 2008. 25. Munnier E, Cohen-Jonathan S, Herve´ K, Linassier C, Souce´ M, Dubois P, Chourpa I. Doxorubicin delivered to MCF-7 cancer cellsby superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity. Journal of Nanoparticle Research. 13: 959-971, 2011. 26. Naqvi S, Samim M, Abdin M, Ahmed F.J, Maitra A, Prashant C, Dinda A.K. Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress. International Journal of Nanomedicine. 5: 983-989, 2010. 27. Kayal S, Ramanujan R.V. Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery. Materials Science and Engineering: C. 30: 484-490, 2010. 28. Shen F, Chu S, Bence A.K, Bailey B, Xue X, Erickson P.A. Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. Journal of Pharmacology and Experimental Therapeutics. 324:95-102, 2008. 29. Shen Y, Tang H, Zhan Y, Van Kirk E.A, Murdoch W.J. Degradable Poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery. Nanomedicine : nanotechnology, biology, and medicine. 5: 192-201, 2009. 30. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecularadvances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews. 56: 185-229, 2004. 31. Mhaidat N.M, Alali F.Q, Matalqah S.M, Matalka II, Jaradat S.A, Al-Sawalha N.A, Thorne R.F. Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78. Anticancer Drugs. 20: 601-606, 2009. 32. Larochelle S. Oxidative damage: A pathway to stress. Nature chemical biology, 12(2), pp.53-53, 2016. 33. Apopa P.L, Qian Y, Shao R, Guo N.L, Schwegler-Berry D, Pacurari M, Porter D, Shi X, Vallyathan V, Castranova V, Flynn D.C. Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling. Particle and Fibre Toxicology. 6: 1, 2009. 34. Ahamed M, Akhtar M.J, Khan M.M, Alhadlaq H.A and Alshamsan A. Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2). Colloids and Surfaces B: Biointerfaces, 148: 665-673, 2016. 35. Choi S.J, Oh J.M, Choy J.H. Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. Journal of Inorganic Biochemistry. 103: 463-471, 2009. 36. Aroui S, Brahim S, De Waard M, Breard J, Kenani A. Efficient induction of apoptosis by doxorubicin coupled to cell-penetrating peptides compared to unconjugated doxorubicin in the human breast cancer cell line MDA-MB 231. Cancer Letters. 285: 28-38, 2009a. 37. Netto C, Toma H.E, Andrade L.H. Superparamagnetic nanoparticles as versatile carriers and supporting materials for enzymes. Journal of Molecular Catalysis B: Enzymatic. 86: 71-92, 2012. 38. Yang Y, Guo Q, Peng J, Su J, Lu X, Zhao Y and Qian Z. Doxorubicin-Conjugated Heparin-Coated Superparamagnetic Iron Oxide Nanoparticles for Combined Anticancer Drug Delivery and Magnetic Resonance Imaging. Journal of Biomedical Nanotechnology, 12(11): 1963-1974, 2016. 39. Mallick N, Anwar M, Asfer M, Mehdi S.H, Rizvi M.M.A, Panda A.K, Talegaonkar S and Ahmad F.J. Chondroitin sulfate-capped super-paramagnetic iron oxide nanoparticles as potential carriers of doxorubicin hydrochloride. Carbohydrate Polymers, 2016. 40. Wei H, Bruns O.T, Chen O and Bawendi M.G. NANOPARTICLES FOR MAGNETIC RESONANCE IMAGING APPLICATIONS. Massachusetts Institute of Technology, U.S. Patent 20,160,074,538, 2016. 41. Xu C, Sun S. New forms of superparamagnetic nanoparticles for biomedical applications. Advanced Drug Delivery Reviews. 65: 732-743, 2012. 42. Mahmoudi M, Simchi A, Imani M, Shokrgozar M.A, Milani A.S, Hafeli U.O, Stroeve P .A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles.Colloids and Surfaces B: Biointerfaces. 75: 300-309, 2010. 43. Kearney A.S. Prodrugs and targeted drug delivery. Advanced Drug Delivery Reviews. 19: 225-239, 1996. 44. Gautier J, Allard-Vannier E, Munnier E, Souc M, Chourpa I. Recent advances in theranostic nanocarriers of doxorubicin based on iron oxide and gold nanoparticles. Journal of Controlled Release. 169: 48-61, 2013.



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