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Sequential Delivery Of Doxorubicin And Zoledronic Acid To Breast Cancer Cells By CB[7]-Modified Iron Oxide Nanoparticles.

F. Benyettou, M. Alhashimi, M. O'Connor, Renu Pasricha, Jérémy Brandel, H. Traboulsi, Javed Mazher, J. Olsen, A. Trabolsi
Published 2017 · Medicine, Materials Science

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Drug-loaded magnetic nanoparticles were synthesized and used for the sequential delivery of the antiresorptive agent zoledronic acid (Zol) and the cytotoxic drug doxorubicin (Dox) to breast cancer cells (MCF-7). Zol was attached to bare iron oxide nanoparticles (IONPs) via phosphonate coordination to form Z-NPs. The unbound imidazole of Zol was then used to complex the organic macrocycle CB[7] to obtain CZ-NPs. Dox was complexed to the CZ-NPs to form the fully loaded particles (DCZ-NPs), which were stable in solution at 37 °C and physiological pH (7.4). Fluorescence spectroscopy established that Dox is released in solution from DCZ-NPs suddenly (i) when the particles are subjected to magnetically induced heating to 42 °C at low pH (5.0) and (ii) in the presence of glutathione (GSH). Mass spectrometry indicated that Zol is released slowly in solution at low pH after Dox release. Magnetic measurements with a magnetic reader revealed that DCZ-NPs are internalized preferentially by MCF-7 cells versus nonmalignant cells (HEK293). Zol and Dox acted synergistically when delivered by the particles. DCZ-NPs caused a decrease in the viability of MCF-7 cells that was greater than the net decrease caused when the drugs were added to the cells individually at concentrations equivalent to those delivered by the particles. MCF-7 cells were treated with DCZ-NPs and subjected to an alternating magnetic field (AMF) which, with the nanoparticles present, raised the temperature of the cells and triggered the intracellular release of Dox, as indicated by fluorescence activated cell sorting (FACS). The cytotoxic effects of the DCZ-NPs on MCF-7 cells were enhanced 10-fold by AMF-induced heating. DCZ-NPs were also able to completely inhibit MCF-7 cell adhesion and invasion in vitro, indicating the potential of the particles to act as antimetastatic agents. Together these results demonstrate that DCZ-NPs warrant development as a system for combined chemo- and thermo-therapeutic treatment of cancer.
This paper references
Apoptosis, Oncosis, and Necrosis
G. Majno (1995)
Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing.
N. Nissen (1998)
10.7150/thno.14858
The Smart Drug Delivery System and Its Clinical Potential
Dong Liu (2016)
10.1038/bcj.2012.10
Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo
T. Kiziltepe (2012)
10.1021/acsami.6b16844
Synergistic Cisplatin/Doxorubicin Combination Chemotherapy for Multidrug-Resistant Cancer via Polymeric Nanogels Targeting Delivery.
Haiqiu Wu (2017)
10.1038/cdd.2013.67
Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer
L. Bracci (2014)
10.1103/PHYSREVB.64.205414
Surface Sensitive Fe 2p Photoemission Spectra for alpha-Fe₂O₃ (0001) - The Influence of Symmetry and Crystal-Field Strength
T. Droubay (2001)
10.1002/CHIN.200413266
Supramolecular Drug‐Delivery Systems Based on Polymeric Core—Shell Architectures.
R. Haag (2004)
10.1016/J.IJROBP.2004.09.065
Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines.
E. Algur (2005)
10.1021/nn501162x
Hyperthermia-mediated local drug delivery by a bubble-generating liposomal system for tumor-specific chemotherapy.
Ko-Jie Chen (2014)
10.1016/j.addr.2011.03.008
Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery.
Challa S. S. R. Kumar (2011)
10.1039/c2cc35131e
Enhanced stability and activity of temozolomide in primary glioblastoma multiforme cells with cucurbit[n]uril.
Eric A. Appel (2012)
10.1158/1078-0432.CCR-07-1545
Differential Effect of Doxorubicin and Zoledronic Acid on Intraosseous versus Extraosseous Breast Tumor Growth In vivo
P. Ottewell (2008)
10.1016/J.BIOMATERIALS.2004.10.012
Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications.
A. Gupta (2005)
10.1006/JCIS.1998.6053
Synthesis of Iron Oxide Nanoparticles Used as MRI Contrast Agents: A Parametric Study.
Babes (1999)
10.1038/sj.bjc.6605604
The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer
R. Coleman (2010)
10.1016/j.chemosphere.2009.04.067
A fluorescence quenching study of the interaction of Suwannee River fulvic acid with iron oxide nanoparticles.
A. Manciulea (2009)
10.1634/theoncologist.2011-0159
Symptom management in metastatic breast cancer.
W. Irvin (2011)
10.1021/JACS.6B09504
Metal-Organic Polyhedron Capped with Cucurbit[8]uril Delivers Doxorubicin to Cancer Cells.
Soumen K Samanta (2016)
10.1002/ijc.20602
Sequence‐ and schedule‐dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells
H. Neville-Webbe (2005)
10.1039/c4cs00273c
Cucurbiturils: from synthesis to high-affinity binding and catalysis.
Khaleel I Assaf (2015)
10.1039/C5MD00365B
Multi-drug delivery nanocarriers for combination therapy
Suresh Gadde (2015)
10.1097/01.CAD.0000175582.01446.6F
Combined effects of zoledronic acid and doxorubicin on breast cancer cell invasion in vitro
J. Woodward (2005)
10.1039/c5nr00295h
Cucurbit[n]uril-capped upconversion nanoparticles as highly emissive scaffolds for energy acceptors.
L. Francés-Soriano (2015)
10.1039/c1cc10721f
Cationic supramolecular nanoparticles for co-delivery of gene and anticancer drug.
Q. Hu (2011)
10.1016/0065-2571(84)90007-4
Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors.
T. Chou (1984)
10.1021/acs.langmuir.6b01433
Redox-Responsive Viologen-Mediated Self-Assembly of CB[7]-Modified Patchy Particles.
F. Benyettou (2016)
10.1016/j.biomaterials.2010.01.123
Hybrid superparamagnetic iron oxide nanoparticle-branched polyethylenimine magnetoplexes for gene transfection of vascular endothelial cells.
R. Namgung (2010)
10.1021/acsami.7b01157
Supramolecular Chemotherapy: Cooperative Enhancement of Antitumor Activity by Combining Controlled Release of Oxaliplatin and Consuming of Spermine by Cucurbit[7]uril.
Yueyue Chen (2017)
Apoptosis, oncosis, and necrosis. An overview of cell death.
G. Majno (1995)
10.1021/acsami.7b00873
Construction of Supramolecular Nanoassembly for Responsive Bacterial Elimination and Effective Bacterial Detection.
Qiaoying Li (2017)
10.1021/acsami.5b08202
Aggregation-Induced-Emissive Molecule Incorporated into Polymeric Nanoparticulate as FRET Donor for Observing Doxorubicin Delivery.
Xiongqi Han (2015)
10.1016/j.cis.2011.04.003
Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles.
S. Laurent (2011)
10.1093/jnci/djn240
Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer.
P. Ottewell (2008)
10.1038/nrc2618
Microenvironmental regulation of metastasis
J. Joyce (2009)
10.1039/C5RA20866A
Interaction Mechanism of Doxorubicin and SWCNT: Protonation and Diameter Effects on the Drug Loading and Releasing.
Y. Wang (2016)
10.1158/0008-5472.CAN-09-1947
Drug combination studies and their synergy quantification using the Chou-Talalay method.
T. Chou (2010)
10.1039/B505641C
A previously unrecognised hydronium di-cation in the crystal structure of a cucurbituril derivative.
I. Bernal (2005)
10.1016/j.ijpharm.2009.04.010
Superparamagnetic nanovector with anti-cancer properties: gamma Fe2O3@Zoledronate.
F. Benyettou (2009)
10.1039/C3TB20852D
Toward theranostic nanoparticles: CB[7]-functionalized iron oxide for drug delivery and MRI.
F. Benyettou (2013)
10.1039/c5lc00994d
A high-throughput mechanofluidic screening platform for investigating tumor cell adhesion during metastasis.
A. Spencer (2016)
10.2147/IJN.S30320
Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers
Wahajuddin (2012)
10.1016/j.biomaterials.2011.08.076
Antibody conjugated magnetic iron oxide nanoparticles for cancer cell separation in fresh whole blood.
Hengyi Xu (2011)
10.1016/j.apsb.2015.03.001
Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment
L. Kang (2015)
10.2147/IJN.S36111
The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles
E. Fröhlich (2012)
10.1088/0957-4484/22/5/055102
Microwave assisted nanoparticle surface functionalization.
F. Benyettou (2011)
10.1016/j.biomaterials.2013.06.046
Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles.
Dian Li (2013)
10.1002/asia.201501434
Emerging Supramolecular Therapeutic Carriers Based on Host-Guest Interactions.
Anis Abdul Karim (2016)
10.1093/toxsci/kfq268
Cell death mechanisms and their implications in toxicology.
S. Orrenius (2011)
10.1021/ar500075g
Stimuli Responsive Systems Constructed Using Cucurbit[n]uril-Type Molecular Containers
L. Isaacs (2014)
10.1002/chem.201405774
Viologen-templated arrays of cucurbit[7]uril-modified iron-oxide nanoparticles.
F. Benyettou (2015)
Design of Organic
T. Skorjanc (2016)
10.4161/cam.36224
An introduction to the wound healing assay using live-cell microscopy
J. Jonkman (2014)
10.1021/JA0319846
Mechanism of host-guest complexation by cucurbituril.
César Marquez (2004)
10.1039/C7RA02693E
Selective growth inhibition of cancer cells with doxorubicin-loaded CB[7]-modified iron-oxide nanoparticles
Farah Benyettou (2017)
In vitro evaluation of zoledronic acid resistance developed in MCF-7 cells.
M. Kars (2007)
10.1016/J.MOLSTRUC.2015.11.039
Influence of the protonation state on the binding mode of methyl orange with cucurbiturils
Suhang He (2016)
10.3389/fphar.2014.00174
Implementation of pharmacokinetic and pharmacodynamic strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research
T. Tuntland (2014)
Supramolecular drug delivery systems : molecular engineering of carrier affinity
Mh Maarten Bakker (2018)
10.1016/J.NANTOD.2014.04.008
Challenges associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A Review of Current Status and Future Prospects.
Sutapa Barua (2014)
10.1002/tcr.201500265
Supramolecular Drug Delivery Systems Based on Water-Soluble Pillar[n]arenes.
Xuan Wu (2016)
10.1002/chem.201605246
Design of Organic Macrocycle-Modified Iron Oxide Nanoparticles for Drug Delivery.
Tina Škorjanc (2017)
10.1016/S1040-8428(00)00078-0
Apoptosis, cell adhesion and the extracellular matrix in the three-dimensional growth of multicellular tumor spheroids.
M. Santini (2000)
10.1038/jcbfm.2009.192
Superparamagnetic Iron Oxide Nanoparticles: Diagnostic Magnetic Resonance Imaging and Potential Therapeutic Applications in Neurooncology and Central Nervous System Inflammatory Pathologies, a Review
J. Weinstein (2010)
10.1021/LA0629781
Phosphonic and sulfonic acid-functionalized gold nanoparticles: a solid-state NMR study.
Petr Fiurášek (2007)
10.1016/j.addr.2010.05.006
Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy.
M. Mahmoudi (2011)
10.1007/S10847-009-9553-6
Host–guest complexes of some cucurbit[n]urils with the hydrochloride salts of some imidazole derivatives
Yan Feng (2009)
10.1039/C5RA22960J
Thermosensitivity profile of malignant glioma U87-MG cells and human endothelial cells following γ-Fe2O3 NPs internalization and magnetic field application
Amel Hanini (2016)
10.1002/smll.201102660
Size-dependent nonlinear weak-field magnetic behavior of maghemite nanoparticles.
Caroline de Montferrand (2012)
10.1016/j.drudis.2012.05.010
Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.
P. Parhi (2012)
10.1016/J.BONE.2005.05.003
Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite.
G. H. Nancollas (2006)
10.1016/J.MOLCATA.2007.08.007
Supramolecular ionic liquids based on host–guest cucurbituril imidazolium complexes
Pedro Montes-Navajas (2008)
10.1002/chem.201602956
Mesoporous γ-Iron Oxide Nanoparticles for Magnetically Triggered Release of Doxorubicin and Hyperthermia Treatment.
F. Benyettou (2016)
10.1158/1535-7163.MCT-09-0462
Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone
P. Ottewell (2009)
10.2147/IJN.S26766
Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy
Hsin-I Chang (2012)
10.1039/C4CE00766B
Cucurbituril/hydroxyapatite based nanoparticles for potential use in theranostic applications
Sunita Prem Victor (2014)
10.3322/caac.20073
Cancer Statistics, 2010
A. Jemal (2010)
10.1021/acs.langmuir.6b02228
Bone-Targeted Mesoporous Silica Nanocarrier Anchored by Zoledronate for Cancer Bone Metastasis.
W. Sun (2016)



This paper is referenced by
10.3390/cancers12071886
Cancer Nanomedicine Special Issue Review Anticancer Drug Delivery with Nanoparticles: Extracellular Vesicles or Synthetic Nanobeads as Therapeutic Tools for Conventional Treatment or Immunotherapy
M. Zocchi (2020)
10.3390/antibiotics7020046
Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity
L. S. Arias (2018)
10.1002/zaac.201900211
Anti‐Tumor Activity of Doxorubicin‐loaded Boehmite Nanocontainers
Carmen Seidl (2019)
10.1016/j.colsurfb.2019.110375
A high-loading drug delivery system based on magnetic nanomaterials modified by hyperbranched phenylboronic acid for tumor-targeting treatment with pH response.
Huijia Song (2019)
10.1007/s00604-020-04354-z
pH-controlled preferential binding of cucurbit[7]uril-coated iron-oxide nanoparticles to 6-mercaptonicotinic acid for fluorescent detection of cadmium ions in the solid state
Reem H. Alzard (2020)
10.3390/jcm8081212
Anti-Tumor Effects of Low Dose Zoledronate on Lung Cancer-Induced Spine Metastasis
Elie Akoury (2019)
10.1557/ADV.2019.156
3D-Printed Nanoporous Scaffolds Impregnated with Zoledronate for the Treatment of Spinal Bone Metastases
Elie Akoury (2019)
10.1002/PPSC.201900112
Clustering of Iron Oxide Nanoparticles with Amphiphilic Invertible Polymer Enhances Uptake and Release of Drugs and MRI Properties
Paige M. Price (2019)
10.1186/s12935-019-0745-x
Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer
Elie Akoury (2019)
10.3390/ijms20092097
Macrocyclic Compounds for Drug and Gene Delivery in Immune-Modulating Therapy
Hongzhen Bai (2019)
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