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SPIONs: Superparamagnetic iron oxide-based nanoparticles for the delivery of microRNAi-therapeutics in cancer

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Abstract

Non-coding RNA (ncRNA)-based therapeutics that induce RNA interference (RNAi), such as microRNAs (miRNAs), have drawn considerable attention as a novel class of targeted cancer therapeutics because of their capacity to specifically target oncogenes/protooncogenes that regulate key signaling pathways involved in carcinogenesis, tumor growth and progression, metastasis, cell survival, proliferation, angiogenesis, and drug resistance. However, clinical translation of miRNA-based therapeutics, in particular, has been challenging due to the ineffective delivery of ncRNA molecules into tumors and their uptake into cancer cells. Recently, superparamagnetic iron oxide-based nanoparticles (SPIONs) have emerged as highly effective and efficient for the delivery of therapeutic RNAs to malignant tissues, as well as theranostic (therapy and diagnostic) applications, due to their excellent biocompatibility, magnetic responsiveness, broad functional surface modification, safety, and biodistribution profiles. This review highlights recent advances in the use of SPIONs for the delivery of ncRNA-based therapeutics with an emphasis on their synthesis and coating strategies. Moreover, the advantages and current limitations of SPIONs and their future perspectives are discussed.

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References

  • M. Abu-Laban, R.R. Kumal, J. Casey, J. Becca, D. LaMaster, C.N. Pacheco, D.G. Sykes, L. Jensen, L.H. Haber, D.J. Hayes, Comparison of thermally actuated retro-diels-alder release groups for nanoparticle based nucleic acid delivery. J. Colloid Interface Sci. 526, 312–321 (2018)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • D. Adams, A. Gonzalez-Duarte, W.D. O’Riordan, C.-C. Yang, M. Ueda, A.V. Kristen, I. Tournev, H.H. Schmidt, T. Coelho, J.L. Berk, Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379(1), 11–21 (2018)

    Article  CAS  PubMed  Google Scholar 

  • T. Ahmad, H. Bae, I. Rhee, Y. Chang, J. Lee, S. Hong, Particle size dependence of relaxivity for silica-coated iron oxide nanoparticles. Curr. Appl. Phys. 12(3), 969–974 (2012)

    Article  ADS  Google Scholar 

  • T. Ahmadzada, G. Reid, D.R. McKenzie, Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer. Biophys. Rev. 10, 69–86 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • N. Ajinkya, X. Yu, P. Kaithal, H. Luo, P. Somani, S. Ramakrishna, Magnetic iron oxide nanoparticle (IONP) synthesis to applications: present and future. Materials 13(20), 4644 (2020)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • H. Akbaba, U. Karagöz, Y. Selamet, A.G. Kantarcı, Synthesis and characterization of cationic lipid coated magnetic nanoparticles using multiple emulsions as microreactors. J. Magn. Magn. Mater. 426, 518–524 (2017)

    Article  ADS  CAS  Google Scholar 

  • A. Ali, H. Zafar, M. Zia, I. ul Haq, A.R. Phull, J.S. Ali, A. Hussain, Synthesis, characterization, applications, and challenges of iron oxide nanoparticles. Nanotechnol. Sci. App. 49–67 (2016)

  • E. Alphandéry, Biodistribution and targeting properties of iron oxide nanoparticles for treatments of cancer and iron anemia disease. Nanotoxicology 13(5), 573–596 (2019)

    Article  PubMed  Google Scholar 

  • E. Alphandéry, Iron oxide nanoparticles for therapeutic applications. Drug Discov. Today 25(1), 141–149 (2020)

    Article  PubMed  Google Scholar 

  • U. Anand, A. Dey, A.K.S. Chandel, R. Sanyal, A. Mishra, D.K. Pandey, V. De Falco, A. Upadhyay, R. Kandimalla, A. Chaudhary, J.K. Dhanjal, Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. (2022)

  • J.H. Arrizabalaga, J.S. Casey, J.C. Becca, Y. Liu, L. Jensen, D.J. Hayes, Development of magnetic nanoparticles for the intracellular delivery of miR-148b in non-small cell lung cancer. Biomed. Eng. Adv. 3, 100031 (2022)

    Article  Google Scholar 

  • A. Avasthi, C. Caro, E. Pozo‑Torres, M.P. Leal, M.L. García‑Martín, Magnetic nanoparticles as MRI contrast agents. Surface-modified Nanobiomater. Electrochem. Biomed. App. l49–91 (2020)

  • K.S. Bhullar, N.O. Lagarón, E.M. McGowan, I. Parmar, A. Jha, B.P. Hubbard, H.V. Rupasinghe, Kinase-targeted cancer therapies: progress, challenges and future directions. Mol. Cancer 17, 1–20 (2018)

    Article  Google Scholar 

  • P.-O. Champagne, H. Westwick, A. Bouthillier, M. Sawan, Colloidal stability of superparamagnetic iron oxide nanoparticles in the central nervous system: a review. Nanomedicine 13(11), 1385–1400 (2018)

    Article  CAS  PubMed  Google Scholar 

  • T. Chan, F. Gu, Development of a colorimetric, superparamagnetic biosensor for the capture and detection of biomolecules. Biosens. Bioelectron. 42, 12–16 (2013)

    Article  CAS  PubMed  Google Scholar 

  • X. Chen, L.S. Mangala, C. Rodriguez-Aguayo, X. Kong, G. Lopez-Berestein, A.K. Sood, RNA interference-based therapy and its delivery systems. Cancer Metastasis Rev. 37, 107–124 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • K. Chen, J. Xie, H. Xu, D. Behera, M.H. Michalski, S. Biswal, A. Wang, X. Chen, Triblock copolymer coated iron oxide nanoparticle conjugate for tumor integrin targeting. Biomaterials. 30(36), 6912–6919 (2009)

  • T. Cristofolini, M. Dalmina, J.A. Sierra, A.H. Silva, A.A. Pasa, F. Pittella, T.B. Creczynski-Pasa, Multifunctional hybrid nanoparticles as magnetic delivery systems for siRNA targeting the HER2 gene in breast cancer cells. Mater. Sci. Eng. C 109(2020)

    Article  CAS  Google Scholar 

  • S.M. Dadfar, K. Roemhild, N.I. Drude, S. von Stillfried, R. Knüchel, F. Kiessling, T. Lammers, Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications. Adv. Drug Deliv. Rev. 138, 302–325 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • F. Danhier, To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? J. Control. Release 244, 108–121 (2016)

    Article  CAS  PubMed  Google Scholar 

  • I. Dasgupta, A. Chatterjee, Recent advances in miRNA delivery systems. Methods Protoc. 4(1), 10 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • V. De Matteis, Exposure to inorganic nanoparticles: routes of entry, immune response, biodistribution and in vitro/in vivo toxicity evaluation. Toxics 5(4), 29 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  • E.B. Denkbaş, E. Celik, E. Erdal, D. Kavaz, Ö. Akbal, G. Kara, C. Bayram Magnetically based nanocarriers in drug delivery. Nanobiomater. Drug Deliv. Elsevier 285–331 (2016)

  • A. Dirisala, S. Uchida, K. Toh, J. Li, S. Osawa, T.A. Tockary, X. Liu, S. Abbasi, K. Hayashi, Y. Mochida, Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines. Sci. Adv. 6(26), eabb8133 (2020)

    Article  ADS  Google Scholar 

  • P. Dong, T. Zhang, H. Xiang, X. Xu, Y. Lv, Y. Wang, C. Lu, Controllable synthesis of exceptionally small-sized superparamagnetic magnetite nanoparticles for ultrasensitive MR imaging and angiography. J. Mater. Chem. B 9(4), 958–968 (2021)

    Article  CAS  PubMed  Google Scholar 

  • J. Dulińska-Litewka, A. Łazarczyk, P. Hałubiec, O. Szafrański, K. Karnas, A. Karewicz, Superparamagnetic iron oxide nanoparticles—Current and prospective medical applications. Materials 12(4), 617 (2019)

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • S. El Sayed, J. Cristante, L. Guyon, J. Denis, O. Chabre, N. Cherradi, MicroRNA therapeutics in cancer: current advances and challenges. Cancers 13, 2680 (2021)

    Article  Google Scholar 

  • R.P. Friedrich, I. Cicha, C. Alexiou, Iron oxide nanoparticles in regenerative medicine and tissue engineering. Nanomaterials 11(9), 2337 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • L.S. Ganapathe, M.A. Mohamed, R. Mohamad Yunus, D.D. Berhanuddin, Magnetite (Fe3O4) nanoparticles in biomedical application: From synthesis to surface functionalisation. Magnetochemistry 6(4), 68 (2020)

    Article  CAS  Google Scholar 

  • A. Ganju, S. Khan, B.B. Hafeez, S.W. Behrman, M.M. Yallapu, S.C. Chauhan, M. Jaggi, miRNA nanotherapeutics for cancer. Drug Discov Today 22(2), 424–432 (2017)

    Article  CAS  PubMed  Google Scholar 

  • Y. Gao, H. Qian, X. Tang, X. Du, G. Wang, H. Zhang, F. Ye, T. Liu, Superparamagnetic iron oxide nanoparticle-mediated expression of miR-326 inhibits human endometrial carcinoma stem cell growth. Int. J. Nanomed. 2719–2731 (2019)

  • S. Guo, L. Huang, Nanoparticles escaping RES and endosome: challenges for siRNA delivery for cancer therapy. J Nanomater 1–12 (2011)

  • M. Gong, H. Liu, N. Sun, Y. Xie, F. Yan, L. Cai, Polyethylenimine-dextran-coated magnetic nanoparticles loaded with miR-302b suppress osteosarcoma in vitro and in vivo. Nanomedicine 15(07), 711–723 (2020)

    Article  CAS  PubMed  Google Scholar 

  • A.K. Gupta, M. Gupta, Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterial 26(18), 3995–4021 (2005)

    Article  CAS  Google Scholar 

  • H. Hosseinkazemi, S. Samani, A. O’Neill, M. Soezi, M. Moghoofei, M.H. Azhdari, F. Aavani, A. Nazbar, S.H. Keshel, M. Doroudian, Applications of iron oxide nanoparticles against breast cancer. J. Nanomater. 2022, 1–12 (2022)

    Article  Google Scholar 

  • S.H. Hu, T.Y. Hsieh, C.S. Chiang, P.J. Chen, Y.Y. Chen, T.L. Chiu, S.Y. Chen, Surfactant-free, lipo-polymersomes stabilized by iron oxide nanoparticles/polymer interlayer for synergistically targeted and magnetically guided gene delivery. Adv. Healthcare Mater. 3(2), 273–282 (2014)

    Article  CAS  Google Scholar 

  • S.R. Iyer, S. Xu, J.P. Stains, C.H. Bennett, R.M. Lovering, Superparamagnetic iron oxide nanoparticles in musculoskeletal biology. Tissue Eng. Part B: Rev. 23(4), 373–385 (2017)

    Article  CAS  PubMed  Google Scholar 

  • L. Jin, Q. Wang, J. Chen, Z. Wang, H. Xin, D. Zhang, Efficient delivery of therapeutic siRNA by Fe3O4 magnetic nanoparticles into oral cancer cells. Pharmaceutics 11(11), 615 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • A. Joseph, S. Mathew, Ferrofluids: synthetic strategies, stabilization, physicochemical features, characterization, and applications. ChemPlusChem 79(10), 1382–1420 (2014)

    Article  MathSciNet  CAS  Google Scholar 

  • G. Kandasamy, D. Maity, Recent advances in superparamagnetic iron oxide nanoparticles (SPIONs) for in vitro and in vivo cancer nanotheranostics. Int. J. Pharm. 496(2), 191–218 (2015)

    Article  CAS  PubMed  Google Scholar 

  • M.A. Kang, J. Fang, A. Paragodaarachchi, K. Kodama, D. Yakobashvili, Y. Ichiyanagi, H. Matsui, Magnetically induced brownian motion of iron oxide nanocages in alternating magnetic fields and their application for efficient SiRNA delivery. Nano Lett. 22(22), 8852–8859 (2022)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • G. Kara, B. Arun, G.A. Calin, B. Ozpolat, miRacle of microRNA-driven cancer nanotherapeutics. Cancers 14(15), 3818 (2022a)

  • G. Kara, G.A. Calin, B. Ozpolat, RNAi-based therapeutics and tumor targeted delivery in cancer. Adv. Drug Deliv. Rev. 182 (2022b)

  • G. Kara, S. Malekghasemi, B. Ozpolat, E.B. Denkbas, Development of novel poly-l-lysine-modified sericin-coated superparamagnetic iron oxide nanoparticles as siRNA carrier. Colloids Surf. A 630 (2021)

  • G. Kara, B. Ozpolat, In vivo miR-449b mimic-based nanotherapy suppresses growth and progression of triple-negative breast cancer. Cancer Res. 83(7_Supplement), 3786–3786 (2023)

    Article  Google Scholar 

  • F.M. Kievit, M. Zhang, Surface engineering of iron oxide nanoparticles for targeted cancer therapy. Acc. Chem. Res. 44(10), 853–862 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • S.J. Kim, B. Lewis, M.S. Steiner, U.V. Bissa, C. Dose, J.A. Frank, Superparamagnetic iron oxide nanoparticles for direct labeling of stem cells and in vivo MRI tracking. Contrast Media Mol. Imaging 11(1), 55–64 (2016)

    Article  CAS  PubMed  Google Scholar 

  • K.M. Krishnan, Biomedical nanomagnetics: a spin through possibilities in imaging, diagnostics, and therapy. IEEE Trans. Magn. 46(7), 2523–2558 (2010)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • P. Krzyszczyk, A. Acevedo, E.J. Davidoff, L.M. Timmins, I. Marrero-Berrios, M. Patel, C. White, C. Lowe, J.J. Sherba, C. Hartmanshenn, The growing role of precision and personalized medicine for cancer treatment. Technology 6(03n04), 79–100 (2018)

    Article  PubMed  Google Scholar 

  • M. Kubovcikova, M. Koneracka, O. Strbak, M. Molcan, V. Zavisova, I. Antal, I. Khmara, D. Lucanska, L. Tomco, M. Barathova, Poly-L-lysine designed magnetic nanoparticles for combined hyperthermia, magnetic resonance imaging and cancer cell detection. J. Magn. Magn. Mater. 475, 316–326 (2019)

    Article  ADS  CAS  Google Scholar 

  • J.K. Lam, M.Y. Chow, Y. Zhang, S.W. Leung, siRNA versus miRNA as therapeutics for gene silencing. Molecular Therapy-Nucleic Acids (2015)

  • N. Lamichhane, M.E. Sharifabad, B. Hodgson, T. Mercer, T. Sen, Superparamagnetic iron oxide nanoparticles (SPIONs) as therapeutic and diagnostic agents (Elsevier, Nanoparticle therapeutics, 2022), pp.455–497

    Google Scholar 

  • S. Laurent, A.A. Saei, S. Behzadi, A. Panahifar, M. Mahmoudi, Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges. Expert Opin. Drug Deliv. 11(9), 1449–1470 (2014)

    Article  CAS  PubMed  Google Scholar 

  • K. Li, H. Nejadnik, H.E. Daldrup-Link, Next-generation superparamagnetic iron oxide nanoparticles for cancer theranostics. Drug Discovery Today 22(9), 1421–1429 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • L. Li, L.-L. Jiang, Y. Zeng, G. Liu, Toxicity of superparamagnetic iron oxide nanoparticles: research strategies and implications for nanomedicine. Chin. Phys. B 22(12)(2013)

    Article  Google Scholar 

  • L. Li, W. Jiang, K. Luo, H. Song, F. Lan, Y. Wu, Z. Gu, Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking. Theranostics 3(8), 595 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  • C. Liang, X. Zhang, Z. Cheng, M. Yang, W. Huang, X. Dong, Magnetic iron oxide nanomaterials: a key player in cancer nanomedicine. View 1(3), 20200046 (2020)

    Article  Google Scholar 

  • V. Llombart, M.R. Mansour, Therapeutic targeting of “undruggable” MYC. EBioMedicine 75 (2022)

  • 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(18), 8554–8565 (2015)

    Article  ADS  CAS  PubMed  Google Scholar 

  • X.J. Loh, T.-C. Lee, Q. Dou, G.R. Deen, Utilising inorganic nanocarriers for gene delivery. Biomater. Sci. 4(1), 70–86 (2016)

    Article  CAS  PubMed  Google Scholar 

  • C.-H. Lu, J.-K. Hsiao, Diagnostic and therapeutic roles of iron oxide nanoparticles in biomedicine. Tzu-Chi Med. J. 35(1), 11 (2023)

    Article  PubMed  Google Scholar 

  • D. Lu, X. Wu, W. Wang, C. Ma, B. Pei, S. Wu, Synthesis and application of Iron Oxide nanoparticles in bone tissue repair. J. Nanomater. 2021, 1–14 (2021)

    Google Scholar 

  • U.M. Mahajan, S. Teller, M. Sendler, R. Palankar, C. van den Brandt, T. Schwaiger, J.-P. Kühn, S. Ribback, G. Glöckl, M. Evert, Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer. Gut 65(11), 1838–1849 (2016)

    Article  CAS  PubMed  Google Scholar 

  • 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(1–2), 24–46 (2011)

    Article  CAS  PubMed  Google Scholar 

  • H. Majeed, V. Gupta, Adverse effects of radiation therapy. (2020)

  • S. Majidi, F. Zeinali Sehrig, S.M. Farkhani, M. Soleymani Goloujeh, A. Akbarzadeh, Current methods for synthesis of magnetic nanoparticles. Artif. Cells Nanomed. Biotechnol. 44(2), 722–734 (2016)

    Article  CAS  PubMed  Google Scholar 

  • L. Maldonado-Camargo, M. Unni, C. Rinaldi, Magnetic characterization of iron oxide nanoparticles for biomedical applications. Biomed. Nanotechnol. Methods Protocols 47–71 (2017)

  • N. Malhotra, J.-S. Lee, R.A.D. Liman, J.M.S. Ruallo, O.B. Villaflores, T.-R. Ger, C.-D. Hsiao, Potential toxicity of iron oxide magnetic nanoparticles: a review. Molecules 25(14), 3159 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • M.T. Manzari, Y. Shamay, H. Kiguchi, N. Rosen, M. Scaltriti, D.A. Heller, Targeted drug delivery strategies for precision medicines. Nat. Rev. Mater. 6(4), 351–370 (2021)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • C. Mattiuzzi, G. Lippi, Current cancer epidemiology. J. Epidemiol. Global Health 9(4), 217 (2019)

    Article  Google Scholar 

  • I. Merinopoulos, T. Gunawardena, C. Stirrat, D. Cameron, S.C. Eccleshall, M.R. Dweck, D.E. Newby, V.S. Vassiliou, Diagnostic applications of ultrasmall superparamagnetic particles of iron oxide for imaging myocardial and vascular inflammation. Cardiovascular Imag. 14(6), 1249–1264 (2021)

    Google Scholar 

  • A. Mittal, I. Roy, S. Gandhi, Magnetic nanoparticles: An overview for biomedical applications. Magnetochemistry 8(9), 107 (2022)

    Article  CAS  Google Scholar 

  • H. Mok, M. Zhang, Superparamagnetic iron oxide nanoparticle-based delivery systems for biotherapeutics. Expert Opin. Drug Deliv. 10(1), 73–87 (2013)

    Article  CAS  PubMed  Google Scholar 

  • M.Y. Momin, R.R. Gaddam, M. Kravitz, A. Gupta, A. Vikram, The challenges and opportunities in the development of MicroRNA therapeutics: a multidisciplinary viewpoint. Cells 10(11), 3097 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • M.G. Montiel Schneider, M.J. Martín, J. Otarola, E. Vakarelska, V. Simeonov, V. Lassalle, M. Nedyalkova, Biomedical applications of iron oxide nanoparticles: Current insights progress and perspectives. Pharmaceutics 14(1), 204 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • V. Mulens-Arias, J.M. Rojas, S. Pérez-Yagüe, M.P. Morales, D.F. Barber, Polyethylenimine-coated SPIONs trigger macrophage activation through TLR-4 signaling and ROS production and modulate podosome dynamics. Biomaterials 52, 494–506 (2015)

    Article  CAS  PubMed  Google Scholar 

  • M. Muthiah, I.-K. Park, C.-S. Cho, Surface modification of iron oxide nanoparticles by biocompatible polymers for tissue imaging and targeting. Biotechnol. Adv. 31(8), 1224–1236 (2013)

    Article  CAS  PubMed  Google Scholar 

  • H.B. Na, I.C. Song, T. Hyeon, Inorganic nanoparticles for MRI contrast agents. Adv. Mater. 21(21), 2133–2148 (2009)

    Article  CAS  Google Scholar 

  • P. Navya, A. Kaphle, S. Srinivas, S.K. Bhargava, V.M. Rotello, H.K. Daima, Current trends and challenges in cancer management and therapy using designer nanomaterials. Nano convergence 6(1), 1–30 (2019)

    Article  CAS  Google Scholar 

  • M.D. Nguyen, H.-V. Tran, S. Xu, T.R. Lee, Fe3O4 Nanoparticles: Structures, synthesis, magnetic properties, surface functionalization, and emerging applications. Appl. Sci. 11(23), 11301 (2021)

    Article  CAS  PubMed  Google Scholar 

  • O.A. Noqta, A.A. Aziz, I.A. Usman, M. Bououdina, Recent advances in iron oxide nanoparticles (IONPs): synthesis and surface modification for biomedical applications. J. Supercond. Novel Magn. 32, 779–795 (2019)

    Article  CAS  Google Scholar 

  • B. Ouyang, W. Poon, Y.-N. Zhang, Z.P. Lin, B.R. Kingston, A.J. Tavares, Y. Zhang, J. Chen, M.S. Valic, A.M. Syed, The dose threshold for nanoparticle tumour delivery. Nat. Mater. 19(12), 1362–1371 (2020)

    Article  ADS  CAS  PubMed  Google Scholar 

  • S. Palanisamy, Y.-M. Wang, Superparamagnetic iron oxide nanoparticulate system: synthesis, targeting, drug delivery and therapy in cancer. Dalton Trans. 48(26), 9490–9515 (2019)

    Article  CAS  PubMed  Google Scholar 

  • Z. Pan, Y. Huang, H. Qian, X. Du, W. Qin, T. Liu, Superparamagnetic iron oxide nanoparticles drive miR-485-5p inhibition in glioma stem cells by silencing Tie1 expression. Int. J. Biol. Sci. 16(7), 1274 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • J. Park, J. Park, Y. Pei, J. Xu, Y. Yeo, Pharmacokinetics and biodistribution of recently-developed siRNA nanomedicines. Adv. Drug Deliv. Rev. 104, 93–109 (2016)

    Article  CAS  PubMed  Google Scholar 

  • K. Paunovska, D. Loughrey, J.E. Dahlman, Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 23(5), 265–280 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • A.K. Pearce, R.K. O’Reilly, Insights into active targeting of nanoparticles in drug delivery: advances in clinical studies and design considerations for cancer nanomedicine. Bioconjug. Chem. 30(9), 2300–2311 (2019)

    Article  CAS  PubMed  Google Scholar 

  • P. Pedrosa, R. Vinhas, A. Fernandes, P.V. Baptista, Gold nanotheranostics: proof-of-concept or clinical tool? Nanomaterials 5(4), 1853–1879 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Y. Peng, Y. Gao, C. Yang, R. Guo, X. Shi, X. Cao, Low-molecular-weight poly (ethylenimine) nanogels loaded with ultrasmall iron oxide nanoparticles for T 1-weighted MR imaging-guided gene therapy of sarcoma. ACS Appl. Mater. Interfaces 13(24), 27806–27813 (2021)

    Article  CAS  PubMed  Google Scholar 

  • M. Perepelyuk, C. Thangavel, Y. Liu, R.B. Den, B. Lu, A.E. Snook, S.A. Shoyele, Biodistribution and pharmacokinetics study of siRNA-loaded anti-NTSR1-mAb-functionalized novel hybrid nanoparticles in a metastatic orthotopic murine lung cancer model. Mol Therapy-Nucleic Acids 5 (2016)

  • S. Prijic, G. Sersa, Magnetic nanoparticles as targeted delivery systems in oncology. Radiol. Oncol. 45(1), 1–16 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • C. Pucci, A. Degl’Innocenti, M.B. Gümüş, G. Ciofani, Superparamagnetic iron oxide nanoparticles for magnetic hyperthermia: Recent advancements, molecular effects, and future directions in the omics era. Biomater. Sci. 10(9), 2103–2121 (2022)

    Article  CAS  PubMed  Google Scholar 

  • M. Rahman, Magnetic Resonance Imaging and Iron-oxide Nanoparticles in the era of Personalized Medicine. Nanotheranostics 7(4), 424 (2023)

    Article  PubMed  PubMed Central  Google Scholar 

  • H. Raskov, A. Orhan, S. Gaggar, I. Gögenur, Cancer-associated fibroblasts and tumor-associated macrophages in cancer and cancer immunotherapy. Front. Oncol. 11(2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • R.A. Revia, Z.R. Stephen, M. Zhang, Theranostic nanoparticles for RNA-based cancer treatment. Acc. Chem. Res. 52(6), 1496–1506 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • J.J. Rychak, A.L. Klibanov, Nucleic acid delivery with microbubbles and ultrasound. Adv. Drug Deliv. Rev. 72, 82–93 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • V. Sachdeva, A. Monga, R. Vashisht, D. Singh, A. Singh, N. Bedi, Iron Oxide Nanoparticles: The precise strategy for targeted delivery of genes, oligonucleotides and peptides in cancer therapy. J. Drug Deliv. Sci. Technol. 103585 (2022)

  • A.V. Samrot, C.S. Sahithya, J. Selvarani, S.K. Purayil, P. Ponnaiah, A review on synthesis, characterization and potential biological applications of superparamagnetic iron oxide nanoparticles. Current Research in Green and Sustainable Chemistry 4(2021)

    Article  CAS  Google Scholar 

  • M. Segal, F.J. Slack, Challenges identifying efficacious miRNA therapeutics for cancer. Expert Opin. Drug Discov. 15(9), 987–991 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  • A. Selimovic, G. Kara, E.B. Denkbas, Magnetic gelatin nanoparticles as a biocompatible carrier system for small interfering RNA in human colorectal cancer: Synthesis, optimization, characterization, and cell viability studies. Mater. Today Commun. 33, 104616 (2022)

    Article  CAS  Google Scholar 

  • D.Y. Seo, M. Jin, J.-C. Ryu, Y.-J. Kim, Investigation of the genetic toxicity by dextran-coated superparamagnetic iron oxide nanoparticles (SPION) in HepG2 cells using the comet assay and cytokinesis-block micronucleus assay. Toxicol. Environ. Heal. Sci. 9, 23–29 (2017)

    Article  Google Scholar 

  • S. Setua, M. Jaggi, M. M. Yallapu, S. C. Chauhan, A. Danilushkina, H. Lee, I. S. Choi, R. Fakhrullin, L. Degli Esposti, A. Tampieri, Targeted and theranostic applications for nanotechnologies in medicine. Nanotechnol. Prevent Regenerative Med. Elsevier 399–511 (2018)

  • A.M.E. Shafey, Green synthesis of metal and metal oxide nanoparticles from plant leaf extracts and their applications: A review. Green Process Synth. 9(1), 304–339 (2020)

    Article  Google Scholar 

  • M.B. Shete, T.S. Patil, A.S. Deshpande, G. Saraogi, N. Vasdev, M. Deshpande, K. Rajpoot, R.K. Tekade, Current trends in theranostic nanomedicines. J Drug Deliv Sci Technol 71, 103280 (2022)

    Article  CAS  Google Scholar 

  • H. Shin, S.J. Park, Y. Yim, J. Kim, C. Choi, C. Won, D.H. Min, Recent advances in RNA therapeutics and RNA delivery systems based on nanoparticles. Advanced Therapeutics 1(7), 1800065 (2018)

    Article  Google Scholar 

  • A. Shirangi, F. Mottaghitalab, S. Dinarvand, F. Atyabi, Theranostic silk sericin/SPION nanoparticles for targeted delivery of ROR1 siRNA: Synthesis, characterization, diagnosis and anticancer effect on triple-negative breast cancer. Int. J. Biol. Macromol. 221, 604–612 (2022)

    Article  CAS  PubMed  Google Scholar 

  • S.A. Smith, L.I. Selby, A.P. Johnston, G.K. Such, The endosomal escape of nanoparticles: toward more efficient cellular delivery. Bioconjug. Chem. 30(2), 263–272 (2018)

    Article  PubMed  Google Scholar 

  • B.K. Sodipo, A.A. Aziz, Recent advances in synthesis and surface modification of superparamagnetic iron oxide nanoparticles with silica. J. Magn. Magn. Mater. 416, 275–291 (2016)

    Article  ADS  CAS  Google Scholar 

  • I. Soerjomataram, F. Bray, Planning for tomorrow: global cancer incidence and the role of prevention 2020–2070. Nat. Rev. Clin. Oncol. 18(10), 663–672 (2021)

    Article  PubMed  Google Scholar 

  • Z. Sohrabijam, M. Saeidifar, A. Zamanian, Enhancement of magnetofection efficiency using chitosan coated superparamagnetic iron oxide nanoparticles and calf thymus DNA. Colloids Surf., B 152, 169–175 (2017)

    Article  CAS  Google Scholar 

  • C. Strehl, L. Maurizi, T. Gaber, P. Hoff, T. Broschard, A. R. Poole, H. Hofmann, F. Buttgereit, Modification of the surface of superparamagnetic iron oxide nanoparticles to enable their safe application in humans. Int. J. Nanomed. 5883–5896 (2016)

  • 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(1), 1092–1109 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • U.K. Sukumar, R.J. Bose, M. Malhotra, H.A. Babikir, R. Afjei, E. Robinson, Y. Zeng, E. Chang, F. Habte, R. Sinclair, Intranasal delivery of targeted polyfunctional gold–iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide. Biomaterials 218(2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Z. Sun, X. Song, X. Li, T. Su, S. Qi, R. Qiao, F. Wang, Y. Huan, W. Yang, J. Wang, In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model. Nanoscale 6(23), 14343–14353 (2014)

    Article  ADS  CAS  PubMed  Google Scholar 

  • Y.K. Sung, S. Kim, Recent advances in the development of gene delivery systems. Biomaterials research 23, 1–7 (2019)

    Article  ADS  Google Scholar 

  • G.M. Traber, A.-M. Yu, RNAi-based therapeutics and novel RNA bioengineering Technologies. J. Pharmacol. Exp. Ther. 384(1), 133–154 (2023)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • N. Usov, Iron oxide nanoparticles for magnetic hyperthermia (World Scientific, Spin, 2019)

    Book  Google Scholar 

  • C. Vasilescu, M. Latikka, K.D. Knudsen, V.M. Garamus, V. Socoliuc, R. Turcu, E. Tombácz, D. Susan-Resiga, R. Ras, L. Vékás, High concentration aqueous magnetic fluids: structure, colloidal stability, magnetic and flow properties. Soft Matter 14(32), 6648–6666 (2018)

    Article  ADS  CAS  PubMed  Google Scholar 

  • O. Veiseh, J.W. Gunn, M. Zhang, Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv. Drug Deliv. Rev. 62(3), 284–304 (2010)

    Article  CAS  PubMed  Google Scholar 

  • N. Wahajuddin, S. Arora, Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int. J. Nanomed. 3445–3471 (2012)

  • Y. Wang, Z. Huang, C.Z. Chen, C. Liu, C.P. Evans, A.C. Gao, F. Zhou, H.-W. Chen, Therapeutic targeting of MDR1 expression by RORγ antagonists resensitizes cross-resistant CRPC to taxane via coordinated induction of cell death programs. Mol. Cancer Ther. 19(2), 364–374 (2020)

    Article  CAS  PubMed  Google Scholar 

  • S. Wilhelm, A.J. Tavares, Q. Dai, S. Ohta, J. Audet, H.F. Dvorak, W.C. Chan, Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1(5), 1–12 (2016)

    Article  Google Scholar 

  • T. Wirth, S. Ylä-Herttuala, Gene therapy used in cancer treatment. Biomedicines 2(2), 149–162 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  • W. Wu, Z. Wu, T. Yu, C. Jiang, W.-S. Kim, Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications. Sci. Technol. Adv. Mater. 16(2)(2015)

    Article  PubMed  PubMed Central  Google Scholar 

  • X. Xiang, J. Wang, D. Lu, X. Xu, Targeting tumor-associated macrophages to synergize tumor immunotherapy. Signal Transduct. Target. Ther. 6(1), 75 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  • Y. Xiao, J. Du, Superparamagnetic nanoparticles for biomedical applications. J. Mater. Chem. B 8(3), 354–367 (2020)

    Article  CAS  PubMed  Google Scholar 

  • J. Xie, S. Lee, X. Chen, Nanoparticle-based theranostic agents. Adv. Drug Deliv. Rev. 62(11), 1064–1079 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Y. Yan, X.-Y. Liu, A. Lu, X.-Y. Wang, L.-X. Jiang, J.-C. Wang, Non-viral vectors for RNA delivery. J. Control. Release 342, 241–279 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Z. Yang, J. Duan, J. Wang, Q. Liu, R. Shang, X. Yang, P. Lu, C. Xia, L. Wang, K. Dou, Superparamagnetic iron oxide nanoparticles modified with polyethylenimine and galactose for siRNA targeted delivery in hepatocellular carcinoma therapy. Int. J. Nanomed. 1851–1865 (2018)

  • Y. Yao, Y. Zhou, L. Liu, Y. Xu, Q. Chen, Y. Wang, S. Wu, Y. Deng, J. Zhang, A. Shao, Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance. Front. Mol. Biosci. 7, 193 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(8), 541–555 (2014)

    Article  CAS  PubMed  Google Scholar 

  • M. Yu, S. Huang, K.J. Yu, A.M. Clyne, Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture. Int. J. Mol. Sci. 13(5), 5554–5570 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Y. Yu, D. Sun, Superparamagnetic iron oxide nanoparticle ‘theranostics’ for multimodality tumor imaging, gene delivery, targeted drug and prodrug delivery. Expert. Rev. Clin. Pharmacol. 3(1), 117–130 (2010)

    Article  CAS  PubMed  Google Scholar 

  • A. Zarepour, A. Zarrabi, A. Khosravi, A. Zarepour, A. Zarrabi, A. Khosravi, Spions as nano-theranostics agents (Springer, 2017)

    Book  Google Scholar 

  • J. Zhang, T. Zhang, J. Gao, Biocompatible iron oxide nanoparticles for targeted cancer gene therapy: A review. Nanomaterials 12(19), 3323 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Y. Zhang, X. Fu, J. Jia, T. Wikerholmen, K. Xi, Y. Kong, J. Wang, H. Chen, Y. Ma, Z. Li, Glioblastoma therapy using codelivery of cisplatin and glutathione peroxidase targeting siRNA from iron oxide nanoparticles. ACS Appl. Mater. Interf. 12(39), 43408–43421 (2020)

    Article  CAS  Google Scholar 

  • S. Zhao, X. Yu, Y. Qian, W. Chen, J. Shen, Multifunctional magnetic iron oxide nanoparticles: an advanced platform for cancer theranostics. Theranostics 10(14), 6278 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Z. Zhao, M. Li, J. Zeng, L. Huo, K. Liu, R. Wei, K. Ni, J. Gao, Recent advances in engineering iron oxide nanoparticles for effective magnetic resonance imaging. Bioactive Mater. 12, 214–245 (2022)

    Article  CAS  Google Scholar 

  • M. Zheng, D. Librizzi, A. Kılıç, Y. Liu, H. Renz, O.M. Merkel, T. Kissel, Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly (ethylene glycol) copolymers. Biomaterials 33(27), 6551–6558 (2012)

    Article  CAS  PubMed  Google Scholar 

  • C. Zhu, X. Guan, X. Zhang, X. Luan, Z. Song, X. Cheng, W. Zhang, J.-J. Qin, Targeting KRAS mutant cancers: from druggable therapy to drug resistance. Mol. Cancer 21(1), 159 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • L. Zhu, Z. Zhou, H. Mao, L. Yang, Magnetic nanoparticles for precision oncology: theranostic magnetic iron oxide nanoparticles for image-guided and targeted cancer therapy. Nanomedicine 12(1), 73–87 (2017)

    Article  CAS  PubMed  Google Scholar 

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Kara, G., Ozpolat, B. SPIONs: Superparamagnetic iron oxide-based nanoparticles for the delivery of microRNAi-therapeutics in cancer. Biomed Microdevices 26, 16 (2024). https://doi.org/10.1007/s10544-024-00698-y

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