Magnetic Nanoparticles for Nucleic Acid Delivery: Magnetofection, Gene Therapy and Vaccines


Magnetic Nanoparticles for Nucleic Acid Delivery: Magnetofection, Gene Therapy and Vaccines

María V. Tuttolomondo, Sofia Municoy, María I. Alvarez Echazú, Lurdes M. López, Gisela S. Alvarez

Gene therapy offers an alternative for the treatment of diseases such as cancer or neurodegenerative diseases by replacing, introducing or inactivating genes in the patient. In this aspect, the use of nanoparticles as nucleic acid delivery systems that prevents its degradation and facilitates its incorporation into target cells has been a subject of intense study in recent years. Among them, magnetic nanoparticles (MNP) offer advantages as new alternatives for non-viral transfection, such as guiding the nanoparticle and its content through magnetic fields towards target organs, increasing the efficiency and reducing transfection times. The use of MNP carrying genetic information to achieve transfection by the application of magnetic fields is known as magnetofection. In most cases, superparamagnetic iron oxide nanoparticles (SPIONs) are used as vehicles which also contain a cationic organic coating to increase their stability, gene incorporation and interaction with cell membranes. Another field in which the application of these new technologies is gaining attention is in the development of DNA and RNA- based vaccines for immunization and immunotherapy. In the following chapter, the use of magnetofection for in vitro experiments as well as the study of in vivo vaccine assays or gene therapy using MNP as nucleic acid carriers, will be discussed.

Nanoparticles, Magnetofection, Vaccines, Gene Therapy, Immunotherapy

Published online , 36 pages

Citation: María V. Tuttolomondo, Sofia Municoy, María I. Alvarez Echazú, Lurdes M. López, Gisela S. Alvarez, Magnetic Nanoparticles for Nucleic Acid Delivery: Magnetofection, Gene Therapy and Vaccines, Materials Research Foundations, Vol. 143, pp 278-313, 2023


Part of the book on Magnetic Nanoparticles for Biomedical Applications

[1] E.M. Materón, C.M. Miyazaki, O. Carr, N. Joshi, P.H.S. Picciani, C.J. Dalmaschio, F. Davis, F.M. Shimizu, Magnetic nanoparticles in biomedical applications: A review, Appl. Surf. Sci. Adv. 6 (2021) 100163.
[2] P. Kush, P. Kumar, R. Singh, A. Kaushik, Aspects of high-performance and bio-acceptable magnetic nanoparticles for biomedical application, Asian J. Pharm. Sci. (2021).
[3] M. Mahmoudi, S. Sant, B. Wang, S. Laurent, T. Sen, Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy, Adv. Drug Deliv. Rev. 63 (2011) 24-46.
[4] P.M. Martins, A.C. Lima, S. Ribeiro, S. Lanceros-Mendez, P. Martins, Magnetic Nanoparticles for Biomedical Applications: From the Soul of the Earth to the Deep History of Ourselves, ACS Appl. Bio Mater. 4 (2021) 5839-5870.
[5] U.S. Ezealigo, B.N. Ezealigo, S.O. Aisida, F.I. Ezema, Iron oxide nanoparticles in biological systems: Antibacterial and toxicology perspective, JCIS Open. (2021) 100027.
[6] A. Ditsch, P.E. Laibinis, D.I.C. Wang, T.A. Hatton, Controlled Clustering and Enhanced Stability of Polymer-Coated Magnetic Nanoparticles, Langmuir. 21 (2005) 6006-6018.
[7] L. Mohammed, H.G. Gomaa, D. Ragab, J. Zhu, Magnetic nanoparticles for environmental and biomedical applications: A review, Particuology. 30 (2017) 1-14.
[8] M.A. Dheyab, A.A. Aziz, M.S. Jameel, O.A. Noqta, P.M. Khaniabadi, B. Mehrdel, Simple rapid stabilization method through citric acid modification for magnetite nanoparticles, Sci. Rep. 10 (2020) 10793.
[9] I. Khmara, O. Strbak, V. Zavisova, M. Koneracka, M. Kubovcikova, I. Antal, V. Kavecansky, D. Lucanska, D. Dobrota, P. Kopcansky, Chitosan-stabilized iron oxide nanoparticles for magnetic resonance imaging, J. Magn. Magn. Mater. 474 (2019) 319-325.
[10] J. Ning, M. Wang, X. Luo, Q. Hu, R. Hou, W. Chen, D. Chen, J. Wang, J. Liu, SiO2 Stabilized Magnetic Nanoparticles as a Highly Effective Catalyst for the Degradation of Basic Fuchsin in Industrial Dye Wastewaters, Molecules. 23 (2018) 2573.
[11] A. Rajan, M. Sharma, N.K. Sahu, Assessing magnetic and inductive thermal properties of various surfactants functionalised Fe3O4 nanoparticles for hyperthermia, Sci. Rep. 10 (2020) 15045.
[12] L.L. Félix, M.A. Rodriguez Martínez, D.G. Pacheco Salazar, J.A. Huamani Coaquira, One-step synthesis of polyethyleneimine-coated magnetite nanoparticles and their structural, magnetic and power absorption study, RSC Adv. 10 (2020) 41807-41815.
[13] S.S. Rohiwal, N. Dvorakova, J. Klima, M. Vaskovicova, F. Senigl, M. Slouf, E. Pavlova, P. Stepanek, D. Babuka, H. Benes, Z. Ellederova, K. Stieger, Polyethylenimine based magnetic nanoparticles mediated non-viral CRISPR/Cas9 system for genome editing, Sci. Rep. 10 (2020) 4619.
[14] S. Rahim, F. Jan Iftikhar, M.I. Malik, Chapter 16 – Biomedical applications of magnetic nanoparticles, in: M.R. Shah, M. Imran, S.B.T.-M.N. for D.D. and D.A. Ullah (Eds.), Micro Nano Technol., Elsevier, 2020: pp. 301-328.
[15] T.J. Daou, G. Pourroy, S. Bégin-Colin, J.M. Grenèche, C. Ulhaq-Bouillet, P. Legaré, P. Bernhardt, C. Leuvrey, G. Rogez, Hydrothermal Synthesis of Monodisperse Magnetite Nanoparticles, Chem. Mater. 18 (2006) 4399-4404.
[16] W. Zhang, F. Shen, R. Hong, Solvothermal synthesis of magnetic Fe3O4 microparticles via self-assembly of Fe3O4 nanoparticles, Particuology. 9 (2011) 179-186.
[17] J. Xu, H. Yang, W. Fu, K. Du, Y. Sui, J. Chen, Y. Zeng, M. Li, G. Zou, Preparation and magnetic properties of magnetite nanoparticles by sol-gel method, J. Magn. Magn. Mater. 309 (2007) 307-311.
[18] I.L. Ardelean, L.B.N. Stoencea, D. Ficai, A. Ficai, R. Trusca, B.S. Vasile, G. Nechifor, E. Andronescu, Development of Stabilized Magnetite Nanoparticles for Medical Applications, J. Nanomater. 2017 (2017) 6514659.
[19] M. Starowicz, P. Starowicz, J. Zukrowski, J. Przewoźnik, A. Lemański, C. Kapusta, J. Banaś, Electrochemical synthesis of magnetic iron oxide nanoparticles with controlled size, J. Nanopart. Res. 13 (2011) 7167-7176.
[20] M.V. Tuttolomondo, M.E. Villanueva, G.S. Alvarez, M.F. Desimone, L.E. Díaz, Preparation of submicrometer monodispersed magnetic silica particles using a novel water in oil microemulsion: Properties and application for enzyme immobilization, Biotechnol. Lett. 35 (2013) 1571-1577.
[21] O. Bomati, M.P. Morales, C.J. Serna, S. Veintemillas, Magnetic nanoparticles prepared by laser-induced pyrolysis, INTERMAG Eur. 2002 – IEEE Int. Magn. Conf. (2002).
[22] R. Eivazzadeh-Keihan, H. Bahreinizad, Z. Amiri, H.A.M. Aliabadi, M. Salimi-Bani, A. Nakisa, F. Davoodi, B. Tahmasebi, F. Ahmadpour, F. Radinekiyan, A. Maleki, M.R. Hamblin, M. Mahdavi, H. Madanchi, Functionalized magnetic nanoparticles for the separation and purification of proteins and peptides, TrAC Trends Anal. Chem. 141 (2021) 116291.
[23] J.R. Sosa-Acosta, J.A. Silva, L. Fernández-Izquierdo, S. Díaz-Castañón, M. Ortiz, J.C. Zuaznabar-Gardona, A.M. Díaz-García, Iron Oxide Nanoparticles (IONPs) with potential applications in plasmid DNA isolation, Colloids Surfaces A Physicochem. Eng. Asp. 545 (2018) 167-178.
[24] A. Ullah Khan, L. Chen, G. Ge, Recent development for biomedical applications of magnetic nanoparticles, Inorg. Chem. Commun. 134 (2021) 108995.
[25] T. Kobayashi, Cancer hyperthermia using magnetic nanoparticles., Biotechnol. J. 6 (2011) 1342-1347.
[26] D. Chang, M. Lim, J.A.C.M. Goos, R. Qiao, Y.Y. Ng, F.M. Mansfeld, M. Jackson, T.P. Davis, M. Kavallaris, Biologically Targeted Magnetic Hyperthermia: Potential and Limitations , Front. Pharmacol. . 9 (2018) 831.
[27] A. Farzin, S.A. Etesami, J. Quint, A. Memic, A. Tamayol, Magnetic Nanoparticles in Cancer Therapy and Diagnosis, Adv. Healthc. Mater. 9 (2020) 1901058.
[28] A. Avasthi, C. Caro, E. Pozo-Torres, M.P. Leal, M.L. García-Martín, Magnetic Nanoparticles as MRI Contrast Agents, Top. Curr. Chem. 378 (2020) 40.
[29] A. Gholami, S.M. Mousavi, S.A. Hashemi, Y. Ghasemi, W.-H. Chiang, N. Parvin, Current trends in chemical modifications of magnetic nanoparticles for targeted drug delivery in cancer chemotherapy., Drug Metab. Rev. 52 (2020) 205-224.
[30] T.K. Kim, J.H. Eberwine, Mammalian cell transfection: the present and the future, Anal. Bioanal. Chem. 397 (2010) 3173-3178.
[31] E. Alphandéry, Iron oxide nanoparticles for therapeutic applications, Drug Discov. Today. 25 (2020) 141-149.
[32] K.J. Widder, A.E. Senyei, D.G. Scarpelli, Magnetic Microspheres: A Model System for Site Specific Drug Delivery in Vivo, Proc. Soc. Exp. Biol. Med. 158 (1978) 141-146.
[33] C.H. Lee, E.Y. Kim, K. Jeon, J.C. Tae, K.S. Lee, Y.O. Kim, M.-Y. Jeong, C.-W. Yun, D.K. Jeong, S.K. Cho, J.H. Kim, H.Y. Lee, K.Z. Riu, S.G. Cho, S.P. Park, Simple, Efficient, and Reproducible Gene Transfection of Mouse Embryonic Stem Cells by Magnetofection, Stem Cells Dev. 17 (2008) 133-142.
[34] F. Scherer, M. Anton, U. Schillinger, J. Henke, C. Bergemann, A. Krüger, B. Gänsbacher, C. Plank, Magnetofection: Enhancing and targeting gene delivery by magnetic force in vitro and in vivo, Gene Ther. 9 (2002) 102-109.
[35] N. Laurent, C. Sapet, L. Le Gourrierec, E. Bertosio, O. Zelphati, Nucleic acid delivery using magnetic nanoparticles: the MagnetofectionTM technology, Ther. Deliv. 2 (2011) 471-482.
[36] J. Estelrich, E. Escribano, J. Queralt, M.A. Busquets, Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery, Int. J. Mol. Sci. 16 (2015).
[37] Y. Wang, H. Cui, K. Li, C. Sun, W. Du, J. Cui, X. Zhao, W. Chen, A magnetic nanoparticle-based multiple-gene delivery system for transfection of porcine kidney cells, PLoS One. 9 (2014) 1-9.
[38] A. AU – Jacquier, V. AU – Risson, L. AU – Schaeffer, Modeling Charcot-Marie-Tooth Disease In Vitro by Transfecting Mouse Primary Motoneurons, JoVE. (2019) e57988.
[39] L. Prosen, B. Markelc, T. Dolinsek, B. Music, M. Cemazar, G. Sersa, Mcam Silencing With RNA Interference Using Magnetofection has Antitumor Effect in Murine Melanoma, Mol. Ther. Nucleic Acids. 3 (2014) e205-e205.
[40] Z. Pan, Z. Shi, H. Wei, F. Sun, J. Song, Y. Huang, T. Liu, Y. Mao, Magnetofection Based on Superparamagnetic Iron Oxide Nanoparticles Weakens Glioma Stem Cell Proliferation and Invasion by Mediating High Expression of MicroRNA-374a, J. Cancer. 7 (2016) 1487-1496.
[41] A. Soledad Pereyra, O. Mykhaylyk, Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells, J. Nanomed. Nanotechnol. 07 (2016).
[42] S. Prijic, L. Prosen, M. Cemazar, J. Scancar, R. Romih, J. Lavrencak, V.B. Bregar, A. Coer, M. Krzan, A. Znidarsic, G. Sersa, Surface modified magnetic nanoparticles for immuno-gene therapy of murine mammary adenocarcinoma., Biomaterials. 33 (2012) 4379-4391.
[43] A. Villanueva, M. Cañete, A.G. Roca, M. Calero, S. Veintemillas-Verdaguer, C.J. Serna, M. del Puerto Morales, R. Miranda, The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells, Nanotechnology. 20 (2009) 115103.
[44] M. Lee, K. Chea, R. Pyda, M. Chua, I. Dominguez, Comparative Analysis of Non-viral Transfection Methods in Mouse Embryonic Fibroblast Cells., J. Biomol. Tech. 28 (2017) 67-74.
[45] Y. Shi, J. Du, L. Zhou, X. Li, Y. Zhou, L. Li, X. Zang, X. Zhang, F. Pan, H. Zhang, Z. Wang, X. Zhu, Size-controlled preparation of magnetic iron oxide nanocrystals within hyperbranched polymers and their magnetofection in vitro, J. Mater. Chem. 22 (2012) 355-360.
[46] Y. Shi, L. Zhou, R. Wang, Y. Pang, W. Xiao, H. Li, Y. Su, X. Wang, B. Zhu, X. Zhu, D. Yan, H. Gu, In situ preparation of magnetic nonviral gene vectors and magnetofection in vitro., Nanotechnology. 21 (2010) 115103.
[47] L. Prosen, M. Čemažar, G. Sersa, Magnetofection: An Effective, Selective and Feasible Non-viral Gene Delivery Method BT – 1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies, in: T. Jarm, P. Kramar (Eds.), Springer Singapore, Singapore, 2016: pp. 335-338.
[48] L. Prosen, S. Prijic, B. Music, J. Lavrencak, M. Cemazar, G. Sersa, Magnetofection: A Reproducible Method for Gene Delivery to Melanoma Cells, Biomed Res. Int. 2013 (2013) 209452.
[49] Y.-L. Lo, H.-L. Chou, Z.-X. Liao, S.-J. Huang, J.-H. Ke, Y.-S. Liu, C.-C. Chiu, L.-F. Wang, Chondroitin sulfate-polyethylenimine copolymer-coated superparamagnetic iron oxide nanoparticles as an efficient magneto-gene carrier for microRNA-encoding plasmid DNA delivery, Nanoscale. 7 (2015) 8554-8565.
[50] L.A. Blokpoel Ferreras, S.Y. Chan, S. Vazquez Reina, J.E. Dixon, Rapidly Transducing and Spatially Localized Magnetofection Using Peptide-Mediated Non-Viral Gene Delivery Based on Iron Oxide Nanoparticles, ACS Appl. Nano Mater. 4 (2021) 167-181.
[51] H.Y. Park, E.H. Noh, H.M. Chung, M.J. Kang, E.Y. Kim, S.P. Park, Efficient Generation of Virus-Free iPS Cells Using Liposomal Magnetofection, PLoS One. 7 (2012).
[52] C.A. Alvizo-Baez, I.E. Luna-Cruz, N. Vilches-Cisneros, C. Rodríguez-Padilla, J.M. Alcocer-González, Systemic delivery and activation of the TRAIL gene in lungs, with magnetic nanoparticles of chitosan controlled by an external magnetic field, Int. J. Nanomedicine. 11 (2016) 6449-6458.
[53] Y.-K. Kim, M. Zhang, J.-J. Lu, F. Xu, B.-A. Chen, L. Xing, H.-L. Jiang, PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier, J. Drug Target. 24 (2016) 457-467.
[54] J. Venero, M. Burguillos, Magnetofection as a new tool to study microglia biology, Neural Regen. Res. 14 (2019) 767-768.
[55] A. Carrillo-Jimenez, M. Puigdellívol, A. Vilalta, J.L. Venero, G.C. Brown, P. StGeorge-Hyslop, M.A. Burguillos, Effective Knockdown of Gene Expression in Primary Microglia With siRNA and Magnetic Nanoparticles Without Cell Death or Inflammation , Front. Cell. Neurosci. . 12 (2018) 313.
[56] T. Umek, T. Olsson, O. Gissberg, O. Saher, E.M. Zaghloul, K.E. Lundin, J. Wengel, E. Hanse, H. Zetterberg, D. Vizlin-Hodzic, C.I.E. Smith, R. Zain, Oligonucleotides Targeting DNA Repeats Downregulate Huntingtin Gene Expression in Huntington’s Patient-Derived Neural Model System., Nucleic Acid Ther. (2021).
[57] A. Hu, X. Chen, Q. Bi, Y. Xiang, R. Jin, H. Ai, Y. Nie, A parallel and cascade control system: magnetofection of miR125b for synergistic tumor-association macrophage polarization regulation and tumor cell suppression in breast cancer treatment, Nanoscale. 12 (2020) 22615-22627.
[58] F. Krötz, C. de Wit, H.Y. Sohn, S. Zahler, T. Gloe, U. Pohl, C. Plank, Magnetofection – A highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo, Mol. Ther. 7 (2003) 700-710.
[59] E. Brett, E.R. Zielins, A. Luan, C.C. Ooi, S. Shailendra, D. Atashroo, S. Menon, C. Blackshear, J. Flacco, N. Quarto, S.X. Wang, M.T. Longaker, D.C. Wan, Magnetic Nanoparticle-Based Upregulation of B-Cell Lymphoma 2 Enhances Bone Regeneration, Stem Cells Transl. Med. 6 (2017) 151-160.
[60] M. Sen, M. Bassetto, F. Poulhes, O. Zelphati, M. Ueffing, B. Arango-Gonzalez, Efficient Ocular Delivery of VCP siRNA via Reverse Magnetofection in RHO P23H Rodent Retina Explants., Pharmaceutics. 13 (2021).
[61] S.M. Shalaby, M.K. Khater, A.M. Perucho, S.A. Mohamed, I. Helwa, A. Laknaur, I. Lebedyeva, Y. Liu, M.P. Diamond, A.A. Al-Hendy, Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells., Fertil. Steril. 105 (2016) 1638-1648.e8.
[62] M. Takafuji, K. Kitaura, T. Nishiyama, S. Govindarajan, V. Gopal, T. Imamura, H. Ihara, Chemically tunable cationic polymer-bonded magnetic nanoparticles for gene magnetofection, J. Mater. Chem. B. 2 (2014) 644-650.
[63] R. Panday, A.M.E. Abdalla, M. Yu, X. Li, C. Ouyang, G. Yang, Functionally modified magnetic nanoparticles for effective siRNA delivery to prostate cancer cells in vitro, J. Biomater. Appl. 34 (2019) 952-964.
[64] C. Sardo, E.F. Craparo, B. Porsio, G. Giammona, G. Cavallaro, Combining Inulin Multifunctional Polycation and Magnetic Nanoparticles: Redox-Responsive siRNA-Loaded Systems for Magnetofection, Polymers (Basel). 11 (2019).
[65] M. Dowaidar, H. Nasser Abdelhamid, M. Hällbrink, Ü. Langel, X. Zou, Chitosan enhances gene delivery of oligonucleotide complexes with magnetic nanoparticles-cell-penetrating peptide, J. Biomater. Appl. 33 (2018) 392-401.
[66] K. Bulaklak, C.A. Gersbach, The once and future gene therapy, Nat. Commun. 11 (2020) 11-14.
[67] E. Papanikolaou, A. Bosio, The Promise and the Hope of Gene Therapy, Front. Genome Ed. 3 (2021) 1-14.
[68] Thomas Blankenstein, Gene Therapy: Principles and Applications, Birkhäuser Basel, Berlin, 2012.
[69] M.R. Cring, V.C. Sheffield, Gene therapy and gene correction: targets, progress, and challenges for treating human diseases, Gene Ther. (2020).
[70] S. Mali, Delivery systems for gene therapy, Indian J. Hum. Genet. 19 (2013) 3-8.
[71] J.T. Bulcha, Y. Wang, H. Ma, P.W.L. Tai, G. Gao, Viral vector platforms within the gene therapy landscape, Signal Transduct. Target. Ther. 6 (2021).
[72] H. Yin, R.L. Kanasty, A.A. Eltoukhy, A.J. Vegas, J.R. Dorkin, D.G. Anderson, Non-viral vectors for gene-based therapy, Nat. Rev. Genet. 15 (2014) 541-555.
[73] M. Ruponen, P. Honkakoski, S. Rönkkö, J. Pelkonen, M. Tammi, A. Urtti, Extracellular and intracellular barriers in non-viral gene delivery, J. Control. Release. 93 (2003) 213-217.
[74] S. Majidi, F. Zeinali Sehrig, M. Samiei, M. Milani, E. Abbasi, K. Dadashzadeh, A. Akbarzadeh, Magnetic nanoparticles: Applications in gene delivery and gene therapy, Artif. Cells, Nanomedicine Biotechnol. 44 (2016) 1186-1193.
[75] J. Dobson, Gene therapy progress and prospects: Magnetic nanoparticle-based gene delivery, Gene Ther. 13 (2006) 283-287.
[76] D.P. Clark, N.J. Pazdernik, Protein Engineering, in: Biotechnology, second, Academic Cell, 2016: pp. 365-392.
[77] J. Dulińska-Litewka, A. Łazarczyk, P. Hałubiec, O. Szafrański, K. Karnas, A. Karewicz, Superparamagnetic iron oxide nanoparticles-current and prospective medical applications, Materials (Basel). 12 (2019) 1-26.
[78] M. Suciu, C.M. Ionescu, A. Ciorita, S.C. Tripon, D. Nica, H. Al-Salami, L. Barbu-Tudoran, Applications of superparamagnetic iron oxide nanoparticles in drug and therapeutic delivery, and biotechnological advancements, Beilstein J. Nanotechnol. 11 (2020) 1092-1109.
[79] A.A. Sizikov, M. V. Kharlamova, M.P. Nikitin, P.I. Nikitin, E.L. Kolychev, Nonviral locally injected magnetic vectors for in vivo gene delivery: A review of studies on magnetofection, Nanomaterials. 11 (2021) 1-17.
[80] C. Vasile, Polymeric Nanomaterials: Recent Developments, Properties and Medical Applications, in: Polym. Nanomater. Nanotherapeutics, Elsevier, 2019: pp. 1-66.
[81] C. Tros de Ilarduya, Y. Sun, N. Düzgüneş, Gene delivery by lipoplexes and polyplexes, Eur. J. Pharm. Sci. 40 (2010) 159-170.
[82] J. Singh, I. Mohanty, S. Rattan, In vivo magnetofection: A novel approach for targeted topical delivery of nucleic acids for rectoanal motility disorders, Am. J. Physiol. – Gastrointest. Liver Physiol. 314 (2018) G109-G118.
[83] OZBIOSCIENCES, PolyMag, (n.d.).
[84] L. Prosen, S. Hudoklin, M. Cemazar, M. Stimac, U. Lampreht Tratar, M. Ota, J. Scancar, R. Romih, G. Sersa, Magnetic field contributes to the cellular uptake for effective therapy with magnetofection using plasmid DNA encoding against Mcam in B16F10 melanoma in vivo, Nanomedicine. 11 (2016) 627-641.
[85] C. Luo, X. Yang, M. Li, H. Huang, Q. Kang, X. Zhang, H. Hui, X. Zhang, C. Cen, Y. Luo, L. Xie, C. Wang, T. He, D. Jiang, T. Li, H. An, A novel strategy for in vivo angiogenesis and osteogenesis: magnetic micro-movement in a bone scaffold, Artif. Cells, Nanomedicine Biotechnol. 46 (2018) 636-645.
[86] V. Singh, P.K. Sharma, M.A. Alam, Role of cationic lipids for the formulation of lipoplexes, Int. J. Res. Pharm. Sci. Technol. 1 (2018) 1-8.
[87] S. Putzke, E. Feldhues, I. Heep, T. Ilg, A. Lamprecht, Cationic lipid/pDNA complex formation as potential generic method to generate specific IRF pathway stimulators, Eur. J. Pharm. Biopharm. 155 (2020) 112-121.
[88] J.L. Bramson, C.A. Bodner, R.W. Graham, Activation of host antitumoral responses by cationic lipid/DNA complexes, Cancer Gene Ther. 7 (2000) 353-359.
[89] M. Buñuales, N. Düzgüne, S. Zalba, M.J. Garrido, C. Tros De Ilarduya, Efficient gene delivery by EGF-lipoplexes in vitro and in vivo, Nanomedicine. 6 (2011) 89-98.
[90] Promega, pGL4.50[luc2/CMV/Hygro] Vector, (n.d.).
[91] Y. Kono, S. Gogatsubo, T. Ohba, T. Fujita, Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field, Drug Deliv. 26 (2019) 935-943.
[92] C. Wang, C. Ding, M. Kong, A. Dong, J. Qian, D. Jiang, Z. Shen, Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo, Biochem. Biophys. Res. Commun. 410 (2011) 537-542.
[93] Q.T.H. Shubhra, A. Oyane, M. Nakamura, S. Puentes, A. Marushima, H. Tsurushima, Rapid one-pot fabrication of magnetic calcium phosphate nanoparticles immobilizing DNA and iron oxide nanocrystals using injection solutions for magnetofection and magnetic targeting, Mater. Today Chem. 6 (2017) 51-61.
[94] Q.T.H. Shubhra, A. Oyane, M. Nakamura, S. Puentes, A. Marushima, H. Tsurushima, Preliminary in vivo magnetofection data using magnetic calcium phosphate nanoparticles immobilizing DNA and iron oxide nanocrystals, Data Br. 18 (2018) 1696-1701.
[95] H.P. Song, J.Y. Yang, S.L. Lo, Y. Wang, W.M. Fan, X.S. Tang, J.M. Xue, S. Wang, Gene transfer using self-assembled ternary complexes of cationic magnetic nanoparticles, plasmid DNA and cell-penetrating tat peptide, Biomaterials. 31 (2010) 769-778.
[96] W. Huang, Z. Liu, G. Zhou, J. Ling, A. Tian, N. Sun, Silencing Bag-1 gene via magnetic gold nanoparticle-delivered siRNA plasmid for colorectal cancer therapy in vivo and in vitro, Tumor Biol. 37 (2016) 10365-10374.
[97] Q.A. Pankhurst, J. Connolly, S.K. Jones, J. Dobson, Applications of magnetic nanoparticles in biomedicine, J. Phys. D. Appl. Phys. 36 (2003) 167-181.
[98] S.D. Xiang, C. Selomulya, J. Ho, V. Apostolopoulos, M. Plebanski, Delivery of DNA vaccines: an overview on the use of biodegradable polymeric and magnetic nanoparticles., Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2 (2010) 205-218.
[99] F.M.N. Al-Deen, S.D. Xiang, C. Ma, K. Wilson, R.L. Coppel, C. Selomulya, M. Plebanski, Magnetic Nanovectors for the Development of DNA Blood-Stage Malaria Vaccines, Nanomater. (Basel, Switzerland). 7 (2017) 30.
[100] X.F. Zhou, B. Liu, X.H. Yu, X. Zha, X.Z. Zhang, X.Y. Wang, Y.H. Jin, Y.G. Wu, C.L. Jiang, Y. Chen, Y. Chen, Y.M. Shan, J.Q. Liu, W. Kong, J.C. Shen, Using magnetic force to enhance immune response to DNA vaccine, Small. 3 (2007) 1707-1713.
[101] C. Plank, O. Zelphati, O.M. Mykhaylyk, Magnetically enhanced nucleic acid delivery. Ten years of magnetofectio�_Progress and prospects_, Adv. Drug Deliv. Rev. 63 (2011) 1300-1331.
[102] F.N. Al-Deen, J. Ho, C. Selomulya, C. Ma, R. Coppel, Superparamagnetic nanoparticles for effective delivery of malaria DNA vaccine., Langmuir. 27 (2011) 3703-3712.
[103] C. Selomulya, Y.Y. Kong, S.D. Xiang, C. Ma, R.L. Coppel, M. Plebanski, Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery FM Nawwab AL-Deen1, Gene Ther. 21 (2014) 212-218.
[104] V.I. Mobarakeh, M.H. Modarressi, P. Rahimi, A. Bolhassani, E. Arefian, Modification of SPION nanocarriers for siRNA delivery: A therapeutic strategy against HIV infection, Vaccine Res. (2019).
[105] S. Kamalzare, Z. Noormohammadi, P. Rahimi, F. Atyabi, S. Irani, F.S.M. Tekie, F. Mottaghitalab, Carboxymethyl dextran-trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV-1 Nef., J. Cell. Physiol. 234 (2019) 20554-20565.
[106] J.H. Erasmus, A.P. Khandhar, M.A. O’Connor, A.C. Walls, E.A. Hemann, P. Murapa, J. Archer, S. Leventhal, J.T. Fuller, T.B. Lewis, K.E. Draves, S. Randall, K.A. Guerriero, M.S. Duthie, D. Carter, S.G. Reed, D.W. Hawman, H. Feldmann, M.J. Gale, D. Veesler, P. Berglund, D.H. Fuller, An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates., Sci. Transl. Med. 12 (2020).
[107] M. Behzadi, B. Vakili, A. Ebrahiminezhad, N. Nezafat, Iron nanoparticles as novel vaccine adjuvants, Eur. J. Pharm. Sci. 159 (2021) 105718.
[108] A.J. Grippin, B. Wummer, T. Wildes, K. Dyson, V. Trivedi, C. Yang, M. Sebastian, H.R. Mendez-Gomez, S. Padala, M. Grubb, M. Fillingim, A. Monsalve, E.J. Sayour, J. Dobson, D.A. Mitchell, Dendritic Cell-Activating Magnetic Nanoparticles Enable Early Prediction of Antitumor Response with Magnetic Resonance Imaging, ACS Nano. 13 (2019) 13884-13898.
[109] B. Yoo, V.C. Jordan, P. Sheedy, A.-M. Billig, A. Ross, P. Pantazopoulos, Z. Medarova, RNAi-Mediated PD-L1 Inhibition for Pancreatic Cancer Immunotherapy, Sci. Rep. 9 (2019) 4712.
[110] Y.-S. Tang, D. Wang, C. Zhou, W. Ma, Y.-Q. Zhang, B. Liu, S. Zhang, Bacterial magnetic particles as a novel and efficient gene vaccine delivery system, Gene Ther. 19 (2012) 1187-1195.
[111] H.A. Schreiber, J. Prechl, H. Jiang, A. Zozulya, Z. Fabry, F. Denes, M. Sandor, Using carbon magnetic nanoparticles to target, track, and manipulate dendritic cells, J. Immunol. Methods. 356 (2010) 47-59.
[112] J. Ho, F.M.N. Al-Deen, A. Al-Abboodi, C. Selomulya, S.D. Xiang, M. Plebanski, G.M. Forde, N,N’-Carbonyldiimidazole-mediated functionalization of superparamagnetic nanoparticles as vaccine carrier., Colloids Surf. B. Biointerfaces. 83 (2011) 83-90.
[113] S. Sungsuwan, Z. Yin, X. Huang, Lipopeptide-Coated Iron Oxide Nanoparticles as Potential Glycoconjugate-Based Synthetic Anticancer Vaccines, ACS Appl. Mater. Interfaces. 7 (2015) 17535-17544.
[114] X.-B. Liu, G.-W. Yu, X.-Y. Gao, J.-L. Huang, L.-T. Qin, H.-B. Ni, C. Lyu, Intranasal delivery of plasmids expressing bovine herpesvirus 1 gB/gC/gD proteins by polyethyleneimine magnetic beads activates long-term immune responses in mice, Virol. J. 18 (2021) 60.
[115] C. Hüttinger, J. Hirschberger, A. Jahnke, R. Köstlin, T. Brill, C. Plank, H. Küchenhoff, S. Krieger, U. Schillinger, Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial., J. Gene Med. 10 (2008) 655-667.