Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Expression and Purification of MamC and Synthesis of BMNPs
2.2. Nanoparticle Characterization
2.3. Oxa–BMNP Nanoassemblies
2.4. Cell Culturing
2.5. In Vitro Proliferation Assays
2.6. Blood Cell Compatibility of MamC-Mediated Magnetite Nanoparticles
2.6.1. Red Blood Cell Assay
2.6.2. White Blood Cell Proliferation Assay
2.6.3. Cell Cytotoxicity of MamC-Mediated Magnetite NPs in RAW 264.7 Cells
2.7. Internalization and Functionality Tests of BMNPs
2.7.1. Cell Staining for Iron Determination
2.7.2. Transmission Electron Microscopy Assays
2.7.3. Cell Migration Assay
2.8. Statistical Analysis
3. Results
3.1. BMNPs and Oxa–BMNP Nanoassemblies
3.2. In Vitro Proliferation Assays
3.3. BMNP Internalization
3.4. Cell Migration under a Magnetic Field In Vitro
3.5. BMNP Biocompatibility in Blood Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Banerjee, A.; Pathak, S.; Subramanium, V.D.; Dharanivasan, G.; Murugesan, R.; Verma, R.S. Strategies for targeted drug delivery in treatment of colon cancer: Current trends and future perspectives. Drug Discov. Today 2017, 22, 1224–1232. [Google Scholar] [CrossRef] [PubMed]
- Simon, K. Colorectal cancer development and advances in screening. Clin. Interv. Aging 2016, 11, 967–976. [Google Scholar] [PubMed]
- Ferlay, J.; Colombet, M.; Soerjomataram, I.; Dyba, T.; Randi, G.; Bettio, M.; Gavin, A.; Visser, O.; Bray, F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur. J. Cancer 2018, 103, 356–387. [Google Scholar] [CrossRef] [PubMed]
- Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018: Cancer Statistics, 2018. CA A Cancer J. Clin. 2018, 68, 7–30. [Google Scholar] [CrossRef] [PubMed]
- Hubbard, J.M.; Grothey, A. Adolescent and young adult colorectal cancer. J. Natl. Compr. Cancer Netw. 2013, 11, 1219–1225. [Google Scholar] [CrossRef]
- Dienstmann, R.; Salazar, R.; Tabernero, J. Personalizing colon cancer adjuvant therapy: Selecting optimal treatments for individual patients. J. Clin. Oncol. 2015, 33, 1787–1796. [Google Scholar] [CrossRef] [PubMed]
- Ychou, M.; Rivoire, M.; Thezenas, S.; Quenet, F.; Delpero, J.-R.; Rebischung, C.; Letoublon, C.; Guimbaud, R.; Francois, E.; Ducreux, M.; et al. A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. The METHEP trial. Ann. Surg. Oncol. 2013, 20, 4289–4297. [Google Scholar] [CrossRef] [PubMed]
- Betsiou, M.; Sikalidis, C.; Papageorgiou, A. Adsorption of oxaliplatin by hydroxyapatite. Bioautomation 2007, 8, 138–145. [Google Scholar]
- Carrato, A.; Gallego, J.; Dı́az-Rubio, E. Oxaliplatin: Results in colorectal carcinoma. Crit. Rev. Oncol. Hematol. 2002, 44, 29–44. [Google Scholar] [CrossRef]
- Betsiou, M.; Bantsis, G.; Zoi, I.; Sikalidis, C. Adsorption and release of gemcitabine hydrochloride and oxaliplatin by hydroxyapatite. Ceram. Int. 2012, 38, 2719–2724. [Google Scholar] [CrossRef]
- Dunn, T.A.; Schmoll, H.J.; Grünwald, V.; Bokemeyer, V.; Casper, J. Comparative cytotoxicity of oxaliplatin and cisplatin in non-seminomatous germ cell cancer cell lines. Investig. New Drugs 1997, 15, 109–114. [Google Scholar] [CrossRef]
- Ades, S. Adjuvant chemotherapy for colon cancer in the elderly: Moving from evidence to practice. Oncology 2009, 23, 162–167. [Google Scholar] [PubMed]
- Kotelevets, L.; Chastre, E.; Desmaële, D.; Couvreur, P. Nanotechnologies for the treatment of colon cancer: From old drugs to new hope. Int. J. Pharm. 2016, 514, 24–40. [Google Scholar] [CrossRef] [PubMed]
- Wang, A.Z.; Langer, R.; Farokhzad, O.C. Nanoparticle delivery of cancer drugs. Annu. Rev. Med. 2012, 63, 185–198. [Google Scholar] [CrossRef] [PubMed]
- Sau, S.; Alsaab, H.O.; Bhise, K.; Alzhrani, R.; Nabil, G.; Iyer, A.K. Multifunctional nanoparticles for cancer immunotherapy: A groundbreaking approach for reprogramming malfunctioned tumor environment. J. Control. Release 2018, 274, 24–34. [Google Scholar] [CrossRef] [PubMed]
- Dobson, J. Magnetic micro- and nano-particle-based targeting for drug and gene delivery. Nanomedicine 2006, 1, 31–37. [Google Scholar] [CrossRef] [PubMed]
- Datta, N.R.; Krishnan, S.; Speiser, D.E.; Neufeld, E.; Kuster, N.; Bodis, S.; Hofmann, H. Magnetic nanoparticle-induced hyperthermia with appropriate payloads: Paul Ehrlich’s “magic (nano)bullet” for cancer theranostics? Cancer Treat. Rev. 2016, 50, 217–227. [Google Scholar] [CrossRef] [PubMed]
- Shubayev, V.I.; Pisanic, T.R.; Jin, S. Magnetic nanoparticles for theragnostics. Adv. Drug Deliv. Rev. 2009, 61, 467–477. [Google Scholar] [CrossRef] [Green Version]
- Pankhurst, Q.A.; Connolly, J.; Jones, S.K.; Dobson, J. Applications of magnetic nanoparticles in biomedicine. J. Phys. D Appl. Phys. 2003, 36, R167–R181. [Google Scholar] [CrossRef] [Green Version]
- Prozorov, T.; Bazylinski, D.A.; Mallapragada, S.K.; Prozorov, R. Novel magnetic nanomaterials inspired by magnetotactic bacteria: Topical review. Mater. Sci. Eng. R Rep. 2013, 74, 133–172. [Google Scholar] [CrossRef]
- Karimi, M.; Ghasemi, A.; Sahandi Zangabad, P.; Rahighi, R.; Moosavi Basri, S.M.; Mirshekari, H.; Amiri, M.; Shafaei Pishabad, Z.; Aslani, A.; Bozorgomid, M.; et al. Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem. Soc. Rev. 2016, 45, 1457–1501. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alphandéry, E.; Faure, S.; Raison, L.; Duguet, E.; Howse, P.A.; Bazylinski, D.A. Heat production by bacterial magnetosomes exposed to an oscillating magnetic field. J. Phys. Chem. C 2011, 115, 18–22. [Google Scholar] [CrossRef]
- Kolhatkar, A.G.; Jamison, A.C.; Litvinov, D.; Willson, R.C.; Lee, T.R. Tuning the magnetic properties of nanoparticles. Int. J. Mol. Sci. 2013, 14, 15977–16009. [Google Scholar] [CrossRef] [PubMed]
- Amemiya, Y.; Arakaki, A.; Staniland, S.S.; Tanaka, T.; Matsunaga, T. Controlled formation of magnetite crystal by partial oxidation of ferrous hydroxide in the presence of recombinant magnetotactic bacterial protein Mms6. Biomaterials 2007, 28, 5381–5389. [Google Scholar] [CrossRef] [PubMed]
- Prozorov, T.; Mallapragada, S.K.; Narasimhan, B.; Wang, L.; Palo, P.; Nilsen-Hamilton, M.; Williams, T.J.; Bazylinski, D.A.; Prozorov, R.; Canfield, P.C. Protein-mediated synthesis of uniform superparamagnetic magnetite nanocrystals. Adv. Funct. Mater. 2007, 17, 951–957. [Google Scholar] [CrossRef]
- Staniland, S.S.; Rawlings, A.E. Crystallizing the function of the magnetosome membrane mineralization protein Mms6. Biochem. Soc. Trans. 2016, 44, 883–890. [Google Scholar] [CrossRef] [Green Version]
- Valverde-Tercedor, C.; Montalbán-López, M.; Perez-Gonzalez, T.; Sanchez-Quesada, M.S.; Prozorov, T.; Pineda-Molina, E.; Fernandez-Vivas, M.A.; Rodriguez-Navarro, A.B.; Trubitsyn, D.; Bazylinski, D.A.; et al. Size control of in vitro synthesized magnetite crystals by the MamC protein of Magnetococcus marinus strain MC-1. Appl. Microbiol. Biotechnol. 2015, 99, 5109–5121. [Google Scholar] [CrossRef]
- Nudelman, H.; Valverde-tercedor, C.; Kolusheva, S.; Perez, T.; Widdrat, M.; Grimberg, N.; Levi, H.; Nelkenbaum, O.; Davidov, G.; Faivre, D.; et al. Structure—Function studies of the magnetite-biomineralizing magnetosome-associated protein MamC. J. Struct. Biol. 2016, 194, 244–252. [Google Scholar] [CrossRef]
- Lopez-Moreno, R.; Fernández-Vivas, A.; Valverde-Tercedor, C.; Azuaga Fortes, A.I.; Casares Atienza, S.; Rodriguez-Navarro, A.B.; Zarivach, R.; Jimenez-Lopez, C. Magnetite nanoparticles biomineralization in the presence of the magnetosome membrane protein MamC: Effect of protein aggregation and protein structure on magnetite formation. Cryst. Growth Des. 2017, 17, 1620–1629. [Google Scholar] [CrossRef]
- García Rubia, G.; Peigneux, A.; Jabalera, Y.; Puerma, J.; Oltolina, F.; Elert, K.; Colangelo, D.; Gómez Morales, J.; Prat, M.; Jimenez-Lopez, C. pH-Dependent adsorption release of doxorubicin on MamC-biomimetic magnetite nanoparticles. Langmuir 2018, 34, 13713–13724. [Google Scholar] [CrossRef] [PubMed]
- Dutta, R.K.; Sahu, S. Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy. Results Pharma Sci. 2012, 2, 38–45. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Munaweera, I.; Shi, Y.; Koneru, B.; Saez, R.; Aliev, A.; Di Pasqua, A.J.; Balkus, K.J. Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer. Mol. Pharm. 2015, 12, 3588–3596. [Google Scholar] [CrossRef] [PubMed]
- Martín, J.D. XPowder, a Software Package for Powder X-ray Diffraction Analysis. Legal Deposit GR 1001/04. 2004. Available online: http://www.xpowder.com (accessed on 5 August 2019).
- Ahmed, K.; Tabuchi, Y.; Kondo, T. Hyperthermia: An effective strategy to induce apoptosis in cancer cells. Apoptosis 2015, 20, 1411–1419. [Google Scholar] [CrossRef] [PubMed]
- Ortiz, R.; Cabeza, L.; Arias, J.L.; Melguizo, C.; Álvarez, P.J.; Vélez, C.; Clares, B.; Áranega, A.; Prados, J. Poly(butylcyanoacrylate) and Poly(ε-caprolactone) Nanoparticles Loaded with 5-Fluorouracil Increase the Cytotoxic Effect of the Drug in Experimental Colon Cancer. AAPS J. 2015, 17, 918–929. [Google Scholar] [CrossRef] [PubMed]
- Evans, B.C.; Nelson, C.E.; Yu, S.S.; Beavers, K.R.; Kim, A.J.; Li, H.; Nelson, H.M.; Giorgio, T.D.; Duvall, C.L. Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J. Vis. Exp. 2013, 73, e50166. [Google Scholar] [CrossRef] [PubMed]
- Assadian, E.; Zarei, M.H.; Gilani, A.G.; Farshin, M.; Degampanah, H.; Pourahmad, J. Toxicity of copper oxide (CuO) nanoparticles on human blood lymphocytes. Biol. Trace Elem. Res. 2017, 184, 350–357. [Google Scholar] [CrossRef] [PubMed]
- Lorente, C.; Cabeza, L.; Clares, B.; Ortiz, R.; Halbaut, L.; Delgado, Á.V.; Perazzoli, G.; Prados, J.; Arias, J.L.; Melguizo, C. Formulation and in vitro evaluation of magnetoliposomes as a potential nanotool in colorectal cancer therapy. Colloids Surf. B Biointerfaces 2018, 171, 553–565. [Google Scholar] [CrossRef] [PubMed]
- Iafisco, M.; Drouet, C.; Adamiano, A.; Pascaud, P.; Montesi, M.; Panseri, S.; Sarda, S.; Tampieri, A. Superparamagnetic iron-doped nanocrystalline apatite as a delivery system for doxorubicin. J. Mater. Chem. B 2016, 4, 57–70. [Google Scholar] [CrossRef]
- Wu, S.; Zhao, X.; Li, Y.; Du, Q.; Sun, J.; Wang, Y.; Wang, X.; Xia, Y.; Wang, Z.; Xia, L. Adsorption properties of doxorubicin hydrochloride onto graphene oxide: Equilibrium, kinetic and thermodynamic studies. Materials 2013, 6, 2026–2042. [Google Scholar] [CrossRef]
- Geisow, M.J.; Evans, W.H. pH in the endosome: Measurements during pinocytosis and receptor-mediated endocytosis. Exp. Cell Res. 1984, 150, 36–46. [Google Scholar] [CrossRef]
- Iglesias, G.R.; Reyes-Ortega, F.; Checa Fernandez, B.L.; Delgado, Á.V. Hyperthermia-Triggered Gemcitabine Release from Polymer-Coated Magnetite Nanoparticles. Polymers 2018, 10, 269. [Google Scholar] [CrossRef] [PubMed]
- Felfoul, O.; Mohammadi, M.; Taherkhani, S.; de Lanauze, D.; Zhong Xu, Y.; Loghin, D.; Essa, S.; Jancik, S.; Houle, D.; Lafleur, M.; et al. Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nat. Nanotechnol. 2016, 11, 941–947. [Google Scholar] [CrossRef] [PubMed]
- Taherkhani, S.; Mohammadi, M.; Daoud, J.; Martel, S.; Tabrizian, M. Covalent Binding of Nanoliposomes to the Surface of Magnetotactic Bacteria for the Synthesis of Self-Propelled Therapeutic Agents. ACS Nano 2014, 8, 5049–5060. [Google Scholar] [CrossRef] [PubMed]
- Manna, P.T.; Obado, S.O.; Boehm, C.; Gadelha, C.; Sali, A.; Chait, B.T.; Rout, M.P.; Field, M.C. Lineage-specific proteins essential for endocytosis in trypanosomes. J. Cell Sci. 2017, 130, 1379–1392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mercanti, V.; Marchetti, A.; Lelong, E.; Perez, F.; Orci, L.; Cosson, P. Transmembrane domains control exclusion of membrane proteins from clathrin-coated pits. J. Cell Sci. 2010, 123, 3329–3335. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bae, J.-E.; Huh, M.-I.; Ryu, B.-K.; Do, J.-Y.; Jin, S.-U.; Moon, M.-J.; Jung, J.-C.; Chang, Y.; Kim, E.; Chi, S.-G.; et al. The effect of static magnetic fields on the aggregation and cytotoxicity of magnetic nanoparticles. Biomaterials 2011, 32, 9401–9414. [Google Scholar] [CrossRef] [PubMed]
- Nosrati, H.; Salehiabar, M.; Manjili, H.K.; Danafar, H.; Davaran, S. Preparation of magnetic albumin nanoparticles via a simple and one-pot desolvation and co-precipitation method for medical and pharmaceutical applications. Int. J. Biol. Macromol. 2018, 108, 909–915. [Google Scholar] [CrossRef] [PubMed]
- White, E.E.; Pai, A.; Weng, Y.; Suresh, A.K.; Van Haute, D.; Pailevanian, T.; Alizadeh, D.; Hajimiri, A.; Badie, B.; Berlin, J.M. Functionalized iron oxide nanoparticles for controlling the movement of immune cells. Nanoscale 2015, 7, 7780–7789. [Google Scholar] [CrossRef] [Green Version]
- Philosof-Mazor, L.; Dakwar, G.R.; Popov, M.; Kolusheva, S.; Shames, A.; Linder, C.; Greenberg, S.; Heldman, E.; Stepensky, D.; Jelinek, R. Bolaamphiphilic vesicles encapsulating iron oxide nanoparticles: New vehicles for magnetically targeted drug delivery. Int. J. Pharm. 2013, 450, 241–249. [Google Scholar] [CrossRef]
- Jin, H.; Qian, Y.; Dai, Y.; Qiao, S.; Huang, C.; Lu, L.; Luo, Q.; Chen, J.; Zhang, Z. Magnetic enrichment of dendritic cell vaccine in lymph node with fluorescent-magnetic nanoparticles enhanced cancer immunotherapy. Theranostics 2016, 6, 2000–2014. [Google Scholar] [CrossRef] [PubMed]
- Lu, Y.-J.; Lin, P.-Y.; Huang, P.-H.; Kuo, C.-Y.; Shalumon, K.T.; Chen, M.-Y.; Chen, J.-P. Magnetic graphene oxide for dual targeted delivery of doxorubicin and photothermal therapy. Nanomaterials 2018, 8, 193. [Google Scholar] [CrossRef] [PubMed]
- Schlenk, F.; Werner, S.; Rabel, M.; Jacobs, F.; Bergemann, C.; Clement, J.H.; Fischer, D. Comprehensive analysis of the in vitro and ex ovo hemocompatibility of surface engineered iron oxide nanoparticles for biomedical applications. Arch. Toxicol. 2017, 91, 3271–3286. [Google Scholar] [CrossRef] [PubMed]
- Lum, J.B.; Infante, A.J.; Makker, D.M.; Yang, F.; Bowman, B.H. Transferrin synthesis by inducer T lymphocytes. J. Clin. Investig. 1986, 77, 841–849. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Chen, B.; Jin, N.; Xia, G.; Chen, Y.; Zhou, Y.; Cai, X.; Ding, J.; Li, X.; Wang, X. The changes of T lymphocytes and cytokines in ICR mice fed with Fe3O4 magnetic nanoparticles. Int. J. Nanomed. 2011, 6, 605–610. [Google Scholar]
- Chen, B.-A.; Jin, N.; Wang, J.; Ding, J.; Gao, C.; Cheng, J.; Xia, G.; Gao, F.; Zhou, Y.; Chen, Y.; et al. The effect of magnetic nanoparticles of Fe3O4 on immune function in normal ICR mice. Int. J. Nanomed. 2010, 5, 593–599. [Google Scholar] [CrossRef]
- Park, E.-J.; Choi, D.-H.; Kim, Y.; Lee, E.-W.; Song, J.; Cho, M.-H.; Kim, J.-H.; Kim, S.-W. Magnetic iron oxide nanoparticles induce autophagy preceding apoptosis through mitochondrial damage and ER stress in RAW264.7 cells. Toxicol. In Vitro 2014, 28, 1402–1412. [Google Scholar] [CrossRef] [PubMed]
- Ilinskaya, A.N.; Dobrovolskaia, M.A. Nanoparticles and the blood coagulation system. Part II: Safety concerns. Nanomedicine 2013, 8, 969–981. [Google Scholar] [CrossRef]
CELL LINE | IC50 FREE OXA | IC50 OXA–BMNPS | IC50 FOLD CHANGE (DECREASE) |
---|---|---|---|
CCD-18 | 0.66 ± 0.06 | 0.40 ± 0.02 | 1.63 |
HCT-15 | 1.91 ± 0.15 | 1.03 ± 0.05 | 1.85 |
HT-29 | 4.15 ± 0.1 | 1.49 ± 0.14 | 2.79 |
MC-38 | 0.49 ± 0.09 | 0.32 ± 0.02 | 1.50 |
T-84 | 4.30 ± 0.15 | 1.92 ± 0.4 | 2.24 |
SW480 | 1.68 ± 0.01 | 0.67 ± 0.05 | 2.52 |
© 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jabalera, Y.; Garcia-Pinel, B.; Ortiz, R.; Iglesias, G.; Cabeza, L.; Prados, J.; Jimenez-Lopez, C.; Melguizo, C. Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics 2019, 11, 395. https://doi.org/10.3390/pharmaceutics11080395
Jabalera Y, Garcia-Pinel B, Ortiz R, Iglesias G, Cabeza L, Prados J, Jimenez-Lopez C, Melguizo C. Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study. Pharmaceutics. 2019; 11(8):395. https://doi.org/10.3390/pharmaceutics11080395
Chicago/Turabian StyleJabalera, Ylenia, Beatriz Garcia-Pinel, Raul Ortiz, Guillermo Iglesias, Laura Cabeza, José Prados, Concepcion Jimenez-Lopez, and Consolación Melguizo. 2019. "Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study" Pharmaceutics 11, no. 8: 395. https://doi.org/10.3390/pharmaceutics11080395