Preparation of Polymer-Stabilized Magnetic Iron Oxide as Selective Drug Nanocarriers to Human Acute Myeloid Leukemia
Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. [email protected]
conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of [email protected]
were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, [email protected]
were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50
values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of [email protected]
as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to [email protected]
 Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater. 2013;12:991-1003.
 Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, et al. Drug delivery systems: An updated review. Int J Pharm Investig. 2012;2:2-11.
 Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. 2007;9:E128-E47.
 Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol. 2006;24:1211-7.
 El-Dakdouki MH, Zhu DC, El-Boubbou K, Kamat M, Chen J, Li W, et al. Development of multifunctional hyaluronan-coated nanoparticles for imaging and drug delivery to cancer cells. Biomacromolecules. 2012;13:1144-51.
 Jain TK, Richey J, Strand M, Leslie-Pelecky DL, Flask CA, Labhasetwar V. Magnetic nanoparticles with dual functional properties: Drug delivery and magnetic resonance imaging. Biomaterials 2008;29:4012-21.
 Dobson J. Magnetic nanoparticles for drug delivery. Drug Dev Res 2006;67:55-60.
 Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev 2008;60:1252-65.
 Sajja HK, East MP, Mao H, Wang YA, Nie S, Yang L. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect. Curr Drug Discovery Technol 2009;6:43-51.
 Yu MK, Jeong YY, Park J, Park S, Kim JW, Min JJ, et al. Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo. Angew Chem, Int Ed 2008;47:5362-5.
 Xie J, Liu G, Eden HS, Ai H, Chen X. Surface-Engineered Magnetic Nanoparticle Platforms for Cancer Imaging and Therapy. Acc Chem Res. 2011;44:883-92.
 Chen B-A, Dai Y-Y, Wang X-M, Zhang R-Y, Xu W-L, Shen H-L, et al. Synergistic effect of the combination of nanoparticulate Fe3O4 and Au with daunomycin on K562/A02 cells. Int J Nanomedicine. 2008;3:343-50.
 Kassab E, Darwish M, Timsah Z, Liu S, Leppla SH, Frankel AE, et al. Cytotoxicity of Anthrax Lethal Toxin to Human Acute Myeloid Leukemia Cells Is Nonapoptotic and Dependent on Extracellular Signal-Regulated Kinase 1/2 Activity. Transl Oncol. 2013;6:25-32.
 O'Brien ME. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15:440-9.
 Hillegass JM, Blumen SR, Cheng K, MacPherson MB, Alexeeva V, Lathrop SA, et al. Increased efficacy of doxorubicin delivered in multifunctional microparticles for mesothelioma therapy. Int J Cancer. 2011;129:233-44.
 Gabizon A, Goren D, Fuks Z, Barenholz Y, Dagan A, Meshorer A. Enhancement of Adriamycin Delivery to Liver Metastatic Cells with Increased Tumoricidal Effect Using Liposomes as Drug Carriers. Cancer Res. 1983;43:4730-5.
 Barenholz Y. Doxil® — The first FDA-approved nano-drug: Lessons learned. J Control Release. 2012;160:117-34.
 El-Boubbou K, Al-Kaysi RO, Al-Muhanna MK, Bahhari HM, Al-Romaeh AI, Darwish N, et al. Ultra-Small Fatty Acid-Stabilized Magnetite Nanocolloids Synthesized by In Situ Hydrolytic Precipitation. Journal of Nanomaterials. 2015:Article ID 620672, 11 pages.
 El-Boubbou K, Ali R, Bahhari HM, AlSaad KO, Nehdi A, Boudjelal M, et al. Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations. Bioconjugate Chem. 2016;27:1471-83.