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In situ hydrogelation systems, such as transdermal polymerization, allow for external control over the gelation processes in a minimally invasive way. Recently, a novel system consisting of near-infrared (NIR) light and plasmonic nanomaterials was demonstrated to cause in vivo transdermal gelation. However, NIR light is not sufficient for gelation induction in deep tissues owing to its limited penetration into tissues. To overcome this problem, here we developed an alternating magnetic field (AMF)-inducible hydrogelation system with superparamagnetic iron oxide nanoparticles (SPIONs), by which a deep-tissue–penetrating AMF can induce heat generation in the SPIONs and temperature elevation (≥ 43 ℃), leading to initiation of thermal polymerization of poly(ethylene glycol) diacrylate. The feasibility of our AMF-inducible hydrogelation was successfully demonstrated using thick porcine muscle tissues (> 2 cm), whereas the NIR light–based hydrogelation system could induce gelation only in tissues thinner than several millimeters. Cell viability assays indicated cytocompatibility of the AMF-inducible hydrogelation for cell encapsulation and delivery. In vivo hydrogelation in rat muscle tissues further validated in situ hydrogelation in deep muscle tissues of a living animal. This AMF-inducible hydrogelation system may overcome the conventional problems of depth limitation and should extend the applicable area of on-demand injectable hydrogel systems for tissue engineering and drug delivery applications.
Schmaljohann, D. Thermo- and pH-responsive polymers in drug delivery. Adv. Drug Deliv. Rev. 2006, 58, 1655–1670.
Stuart, M. A. C.; Huck, W. T. S.; Genzer, J.; Müller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukruk, V. V.; Urban, M. et al. Emerging applications of stimuliresponsive polymer materials. Nat. Mater. 2010, 9, 101–113.
Reddy, N. N.; Ravindra, S.; Reddy, N. M.; Rajinikanth, V.; Raju, K. M.; Vallabhapurapu, V. S. Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications. J. Magn. Magn. Mater. 2015, 394, 237–244.
Liu, Z.; Tabakman, S.; Welsher, K.; Dai, H. J. Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery. Nano Res. 2009, 2, 85–120.
Tous, E.; Purcell, B.; Ifkovits, J. L.; Burdick, J. A. Injectable acellular hydrogels for cardiac repair. J. Cardiovasc. Transl. Res. 2011, 4, 528–542.
Pehlivaner Kara, M. O.; Ekenseair, A. K. Free epoxide content mediates encapsulated cell viability and activity through protein interactions in a thermoresponsive, in situ forming hydrogel. Biomacromolecules 2017, 18, 1473–1481.
Zheng, Y. H.; Cheng, Y. L.; Chen, J. J.; Ding, J. X.; Li, M. Q.; Li, C.; Wang, J. C.; Chen, X. S. Injectable hydrogelmicrosphere construct with sequential degradation for locally synergistic chemotherapy. ACS Appl. Mater. Interfaces 2017, 9, 3487–3496.
Ye, Y. Q.; Wang, C.; Zhang, X. D.; Hu, Q. Y.; Zhang, Y. Q.; Liu, Q.; Wen, D.; Milligan, J.; Bellotti, A.; Huang, L. et al. A melanin-mediated cancer immunotherapy patch. Sci. Immunol. 2017, 2, eaan5692.
Lee, H.; Chung, S.; Kim, M. G.; Lee, L. P.; Lee, J. Y. Near-infrared-light-assisted photothermal polymerization for transdermal hydrogelation and cell delivery. Adv. Healthc. Mater. 2016, 5, 1638–1645.
Liu, R.; Chen, H.; Li, Z. Q.; Shi, F.; Liu, X. Y. Extremely deep photopolymerization using upconversion particles as internal lamps. Polym. Chem. 2016, 7, 2457–2463.
Gramlich, W. M.; Holloway, J. L.; Rai, R.; Burdick, J. A. Transdermal gelation of methacrylated macromers with near-infrared light and gold nanorods. Nanotechnology 2014, 25, 014004.
Ntziachristos, V.; Bremer, C.; Weissleder, R. Fluorescence imaging with near-infrared light: New technological advances that enable in vivo molecular imaging. Eur. Radiol. 2003, 13, 195–208.
Wang, S. H.; Riedinger, A.; Li, H. B.; Fu, C. H.; Liu, H. Y.; Li, L. L.; Liu, T. L.; Tan, L. F.; Barthel, M. J.; Pugliese, G. et al. Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects. ACS Nano 2015, 9, 1788–1800.
Huang, X. H.; El-Sayed, M. A. Gold nanoparticles: Optical properties and implementations in cancer diagnosis and photothermal therapy. J. Adv. Res. 2010, 1, 13–28.
Hudson, D. E.; Hudson, D. O.; Wininger, J. M.; Richardson, B. D. Penetration of laser light at 808 and 980 nm in bovine tissue samples. Photomed. Laser Surg. 2013, 31, 163–168.
Stolik, S.; Delgado, J. A.; Pérez, A.; Anasagasti, L. Measurement of the penetration depths of red and near infrared light in human "ex vivo" tissues. J. Photochem. Photobiol. B 2000, 57, 90–93.
Melo, C. A. S.; Lima, A. L. L. A.; Brasil, I. R. C.; Silva, O. C. E., Jr.; Magalhães, D. V.; Marcassa, L. G.; Bagnato, V. S. Characterization of light penetration in rat tissues. J. Clin. Laser Med. Surg. 2001, 19, 175–179.
Mornet, S.; Vasseur, S.; Grasset, F.; Duguet, E. Magnetic nanoparticle design for medical diagnosis and therapy. J. Mater. Chem. 2004, 14, 2161–2175.
Olsvik, O.; Popovic, T.; Skjerve, E.; Cudjoe, K. S.; Hornes, E.; Ugelstad, J.; Uhlén, M. Magnetic separation techniques in diagnostic microbiology. Clin. Microbiol. Rev. 1994, 7, 43–54.
Neuberger, T.; Schöpf, B.; Hofmann, H.; Hofmann, M.; Von Rechenberg, B. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system. J. Magn. Magn. Mater. 2005, 293, 483–496.
Reddy, L. H.; Arias, J. L.; Nicolas, J.; Couvreur, P. Magnetic nanoparticles: Design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chem. Rev. 2012, 112, 5818–5878.
Ma, X. H.; Gong, A.; Chen, B.; Zheng, J. J.; Chen, T. X.; Shen, Z. Y.; Wu, A. G. Exploring a new SPION-based MRI contrast agent with excellent water-dispersibility, high specificity to cancer cells and strong MR imaging efficacy. Colloids Surf. B Biointerfaces 2015, 126, 44–49.
Borges, M.; Yu, S.; Laromaine, A.; Roig, A.; Suárez-García, S.; Lorenzo, J.; Ruiz-Molina, D.; Novio, F. Dual T1/T2 MRI contrast agent based on hybrid SPION@coordination polymer nanoparticles. RSC Adv. 2015, 5, 86779–86783.
Szpak, A.; Fiejdasz, S.; Prendota, W.; Strączek, T.; Kapusta, C.; Szmyd, J.; Nowakowska, M.; Zapotoczny, S. T1–T2 dual-modal MRI contrast agents based on superparamagnetic iron oxide nanoparticles with surface attached gadolinium complexes. J. Nanoparticle Res. 2014, 16, 2678.
Fortin, J. P.; Gazeau, F.; Wilhelm, C. Intracellular heating of living cells through Néel relaxation of magnetic nanoparticles. Eur. Biophys. J. 2008, 37, 223–228.
Hudson, R. Coupling the magnetic and heat dissipative properties of Fe3O4 particles to enable applications in catalysis, drug delivery, tissue destruction and remote biological interfacing. RSC Adv. 2016, 6, 4262–4270.
Hayashi, K.; Nakamura, M.; Sakamoto, W.; Yogo, T.; Miki, H.; Ozaki, S.; Abe, M.; Matsumoto, T.; Ishimura, K. Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment. Theranostics 2013, 3, 366–376.
Johannsen, M.; Thiesen, B.; Wust, P.; Jordan, A. Magnetic nanoparticle hyperthermia for prostate cancer. Int. J. Hyperthermia 2010, 26, 790–795.
Gao, F. P.; Cai, Y. Y.; Zhou, J.; Xie, X. X.; Ouyang, W. W.; Zhang, Y. H.; Wang, X. F.; Zhang, X. D.; Wang, X. W.; Zhao, L. Y. et al. Pullulan acetate coated magnetite nanoparticles for hyper-thermia: Preparation, characterization and in vitro experiments. Nano Res. 2010, 3, 23–31.
Zhang, Z. Q.; Song, S. C. Multiple hyperthermia-mediated release of TRAIL/SPION nanocomplex from thermosensitive polymeric hydrogels for combination cancer therapy. Biomaterials 2017, 132, 16–27.
Espinosa, A.; Di Corato, R.; Kolosnjaj-Tabi, J.; Flaud, P.; Pellegrino, T.; Wilhelm, C. Duality of iron oxide nanoparticles in cancer therapy: Amplification of heating efficiency by magnetic hyperthermia and photothermal bimodal treatment. ACS Nano 2016, 10, 2436–2446.
Sivakumar, B.; Aswathy, R. G.; Romero-Aburto, R.; Mitcham, T.; Mitchel, K. A.; Nagaoka, Y.; Bouchard, R. R.; Ajayan, P. M.; Maekawa, T.; Sakthikumar, D. N. Highly versatile SPION encapsulated PLGA nanoparticles as photothermal ablators of cancer cells and as multimodal imaging agents. Biomater. Sci. 2017, 5, 432–443.
Ma, X. X.; Tao, H. Q.; Yang, K.; Feng, L. Z.; Cheng, L.; Shi, X. Z.; Li, Y. G.; Guo, L.; Liu, Z. A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging. Nano Res. 2012, 5, 199–212.
Xing, R. J.; Bhirde, A. A.; Wang, S. J.; Sun, X. L.; Liu, G.; Hou, Y. L.; Chen, X. Y. Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles. Nano Res. 2013, 6, 1–9.
Yallapu, M. M.; Foy, S. P.; Jain, T. K.; Labhasetwar, V. PEG-functionalized magnetic nanoparticles for drug delivery and magnetic resonance imaging applications. Pharm. Res. 2010, 27, 2283–2295.
Jeon, H.; Kim, J.; Lee, Y. M.; Kim, J.; Choi, H. W.; Lee, J.; Park, H.; Kang, Y.; Kim, I. S.; Lee, B. H. et al. Polypaclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system. J. Control. Release 2016, 231, 68–76.
Rose, L. C.; Bear, J. C.; McNaughter, P. D.; Southern, P.; Piggott, R. B.; Parkin, I. P.; Qi, S.; Mayes, A. G. A SPIONeicosane protective coating for water soluble capsules: Evidence for on-demand drug release triggered by magnetic hyperthermia. Sci. Rep. 2016, 6, 20271.
Wei, Y. S.; Liao, R. F.; Mahmood, A. A.; Xu, H. B.; Zhou, Q. B. pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent. Acta Biomater. 2017, 55, 194–203.
Yu, J.; Hao, R.; Sheng, F. G.; Xu, L. L.; Li, G. J.; Hou, Y. L. Hollow manganese phosphate nanoparticles as smart multifunctional probes for cancer cell targeted magnetic resonance imaging and drug delivery. Nano Res. 2012, 5, 679–694.
Wu, M.; Zhang, D.; Zeng, Y. Y.; Wu, L. J.; Liu, X. L.; Liu, J. F. Nanocluster of superparamagnetic iron oxide nanoparticles coated with poly (dopamine) for magnetic field-targeting, highly sensitive MRI and photothermal cancer therapy. Nanotechnology 2015, 26, 115102.
Jin, Z. K.; Wen, Y. Y.; Hu, Y. X.; Chen, W. W.; Zheng, X. F.; Guo, W. S.; Wang, T. F.; Qian, Z. Y.; Su, B. L.; He, Q. J. MRI-guided and ultrasound-triggered release of NO by advanced nanomedicine. Nanoscale 2017, 9, 3637–3645.
Sau, T. K.; Murphy, C. J. Seeded high yield synthesis of short Au nanorods in aqueous solution. Langmuir 2004, 20, 6414–6420.
Eghtedari, M.; Oraevsky, A.; Copland, J. A.; Kotov, N. A.; Conjusteau, A.; Motamedi, M. High sensitivity of in vivo detection of gold nanorods using a laser optoacoustic imaging system. Nano Lett. 2007, 7, 1914–1918.
Yang, K.; Peng, H. B.; Wen, Y. H.; Li, N. Re-examination of characteristic FTIR spectrum of secondary layer in bilayer oleic acid-coated Fe3O4 nanoparticles. Appl. Surf. Sci. 2010, 256, 3093–3097.
Jin, X. M.; Liang, J. L.; Yang, C. F.; Hao, R. J.; Zhuang, J. Q.; Yang, W. S. Facile deposition of continuous gold shells on Tween-20 modified Fe3O4 superparticles. J. Mater. Chem. B 2013, 1, 1921–1925.
Kwon, S.; Ki, S. M.; Park, S. E.; Kim, M. J.; Hyung, B.; Lee, N. K.; Shim, S.; Choi, B. O.; Na, D. L.; Lee, J. E. et al. Anti-apoptotic effects of human Wharton's Jelly-derived mesenchymal stem cells on skeletal muscle cells mediated via secretion of XCL1. Mol. Ther. 2016, 24, 1550–1560.
Obaidat, I. M.; Issa, B.; Haik, Y. Magnetic properties of magnetic nanoparticles for efficient hyperthermia. Nanomaterials 2015, 5, 63–89.
Gupta, A. K.; Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005, 26, 3995–4021.
Bottomley, P. A.; Andrew, E. R. RF magnetic field penetration, phase shift and power dissipation in biological tissue: Implications for NMR imaging. Phys. Med. Biol. 1978, 23, 630–643.
Jordan, A.; Scholz, R.; Wust, P.; Fähling, H.; Felix, R. Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles. J. Magn. Magn. Mater. 1999, 201, 413–419.
Stile, R. A.; Healy, K. E. Thermo-responsive peptide-modified hydrogels for tissue regeneration. Biomacromolecules 2001, 2, 185–194.
Benoit, D. S. W.; Durney, A. R.; Anseth, K. S. The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation. Biomaterials 2007, 28, 66–77.
Nuttelman, C. R.; Tripodi, M. C.; Anseth, K. S. In vitro osteogenic differentiation of human mesenchymal stem cells photoencapsulated in PEG hydrogels. J. Biomed. Mater. Res. A 2004, 68, 773–782.
Steinmetz, N. J.; Bryant, S. J. The effects of intermittent dynamic loading on chondrogenic and osteogenic differentiation of human marrow stromal cells encapsulated in RGD-modified poly(ethylene glycol) hydrogels. Acta Biomater. 2011, 7, 3829–3840.
Nuttelman, C. R.; Benoit, D. S. W.; Tripodi, M. C.; Anseth, K. S. The effect of ethylene glycol methacrylate phosphate in PEG hydrogels on mineralization and viability of encapsulated hMSCs. Biomaterials 2006, 27, 1377–1386.
Wang, Q. W.; Chen, B.; Cao, M.; Sun, J. F.; Wu, H.; Zhao, P.; Xing, J.; Yang, Y.; Zhang, X. Q.; Ji, M. et al. Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials 2016, 86, 11–20.
Wang, Q. W.; Chen, B.; Ma, F.; Lin, S. K.; Cao, M.; Li, Y.; Gu, N. Magnetic iron oxide nanoparticles accelerate osteogenic differentiation of mesenchymal stem cells via modulation of long noncoding RNA INZEB2. Nano Res. 2017, 10, 626–642.
Hergt, R.; Dutz, S. Magnetic particle hyperthermia— biophysical limitations of a visionary tumour therapy. J. Magn. Magn. Mater. 2007, 311, 187–192.
Guardia, P.; Di Corato, R.; Lartigue, L.; Wilhelm, C.; Espinosa, A.; Garcia-Hernandez, M.; Gazeau, F.; Manna, L.; Pellegrino, T. Water-soluble iron oxide nanocubes with high values of specific absorption rate for cancer cell hyperthermia treatment. ACS Nano 2012, 6, 3080–3091.