Abstract
Nanostructure-based materials for multimodal imaging have attracted great attentions. Here we report a new formulation integrated gadolinium (Gd) and magnetite (Fe3O4) nanoparticles as magnetic resonance (MR) imaging contrast agent at both T1 mode and T2 mode. Polyetherimide coated iron oxide (Fe3O4@PEI) nanoparticles were first synthesized and then conjugated to diethylenetriamine pentaacetic acid (DTPA), which further chelated with Gd3+ ions (Fe3O4@PEI@DTPA-Gd). Both phantom and MR studies showed Fe3O4@PEI@DTPA-Gd nanocomposites could be applied in two modes (r1 = 4.7 mM−1 s−1, r2 = 131.82 mM−1 s−1). MTT and fluorescent staining results also suggested that the nanocomposites had good biocompatibility. Besides, Fe3O4@PEI@DTPA-Gd nanocomposites exhibited high entrap efficiency when the mass ratio of nanocomposites to DNA was up to 30:1. The in vitro gene transfection ability was also evidenced. Therefore, Fe3O4@PEI@DTPA-Gd nanocomposites can be employed as a potential candidate for MRI guided clinical diagnosis and gene delivery guided therapy.
Similar content being viewed by others
References
Bae KH, Kim YB, Lee Y, Hwang J, Park H, Park TG (2010) Bioinspired synthesis and characterization of gadolinium-labeled magnetite nanoparticles for dual contrast T1- and T2-weighted magnetic resonance imaging. Bioconjug Chem 21:505–512
Barbieri A, Weiss W, Van Hove MA, Somorjai GA (1994) Magnetite Fe3O4 (111): surface structure by LEED crystallography and energetics. Surf Sci 302:259–279
Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499
Cai H, An X, Cui J, Li J, Wen S, Li K et al (2013) Facile hydrothermal synthesis and surface functionalization of polyethyleneimine-coated iron oxide nanoparticles for biomedical applications. ACS Appl Mater Interfaces 5:1722–1731
Chen Y, Chen HR, Zeng DP, Tian YB, Chen F, Feng JW et al (2010a) Core/shell structured hollow mesoporous nanocapsules: a potential platform for simultaneous cell imaging and anticancer drug delivery. ACS Nano 4:6001–6013
Chen DY, Jiang MJ, Li NJ, Gu HW, Xu QF, Ge JF et al (2010b) Modification of magnetic silica/iron oxide nanocomposites with fluorescent polymethacrylic acid for cancer targeting and drug delivery. J Mater Chem 20:6422–6429
Chourpa I, Douziech-Eyrolles L, Ngaboni-Okassa L, Fouquenet JF, Cohen-Jonathan S, Soucé M et al (2005) Molecular composition of iron oxide nanoparticles, precursors for magnetic drug targeting, as characterized by confocal Raman microspectroscopy. Analyst 130:1395–1403
Kim J, Piao Y, Hyeon T (2009) Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. Chem Soc Rev 38:372–390
Lee H, Lee E, Kim DK, Jang NK, Jeong YY, Jon S (2006) Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. J Am Chem Soc 128:7383–7389
Lee HY, Li Z, Chen K, Hsu AR, Xu C, Xie J et al (2008) PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles. J Nucl Med 49:1371–1379
Li F, Zhi D, Luo Y, Zhang J, Nan X, Zhang Y et al (2016) Core/shell F Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents. Nanoscale 8:12826–12833
Ma LL, Feldman MD, Tam JM, Paranjape AS, Cheruku KK, Larson TA et al (2009) Small multifunctional nanoclusters (nanoroses) for targeted cellular imaging and therapy. ACS Nano 3:2686–2696
Moore A, Medarova Z, Potthast A, Dai G (2004) In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe. Cancer Res 64:1821–1827
Ogris M, Brunner S, Schüller S, Kircheis R, Wagner E (1999) PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther 6:595–605
Parekh G, Shi YY, Zheng JJ, Zhang XC, Leporatti S (2018) Nano-carriers for targeted delivery and biomedical imaging enhancement. Ther Deliv 9:451–468
Parveen S, Misra R, Sahoo SK (2012) Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine 8:147–166
Reddy LH, Arias JL, Nicolas J, Couvreur P (2012) Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chem Rev 112:5818–5878
Shebanova ON, Lazor P (2003) Raman spectroscopic study of magnetite (FeFe2O4): a new assignment for the vibrational spectrum. J Solid State Chem 174:424–430
Shen J, Li Y, Zhu Y, Yang X, Yao X, Li J et al (2015) Multifunctional gadolinium-labeled silica-coated Fe3O4 and CuInS2 nanoparticles as a platform for in vivo tri-modality magnetic resonance and fluorescence imaging. J Mater Chem B 3:2873–2882
Song MM, Xiang HH, Fei MY, Lu DP, Jiang TC, Yu YQ et al (2018) Facile fabrication of water-dispersible nanocomposites based on hexa- hexabenzocoronene and Fe3O4 for dual mode imaging (fluorescent/MR) and drug delivery. RSC Adv 8:40554–40563
Song XW, Yan GH, Quan SS, Jin EH, Quan JS, Jin GY (2019) MRI-visible liposome–polyethylenimine complexes for DNA delivery: preparation and evaluation. Biosci Biotechnol Biochem 83:622–632
Tegafaw T, Xu WL, Ahmad MW, Baeck JS, Chang YM, Bae JE et al (2015) Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application. Nanotechnology 26:365102
Terreno E, Delli Castelli D, Viale A, Aime S (2010) Challenges for molecular magnetic resonance imaging. Chem Rev 110:3019–3042
Vergaro V, Scarlino F, Bellomo C, Rinaldi R, Vergara D, Maffia M et al (2011) Drug-loaded polyelectrolyte microcapsules for sustained targeting of cancer cells. Adv Drug Deliv Rev 63:847–864
Wang Y, Cui HX, Li K, Sun CJ, Du W, Cui JH et al (2014) A magnetic nanoparticle-based multiple-gene delivery system for transfection of porcine kidney cells. PLoS One 9:e102886
Wightman L, Kircheis R, Rössler V, Carotta S, Ruzicka R, Kursa M et al (2001) Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo. J. Gene Med 3:362–372
Xia YN (2008) Nanomaterials at work in biomedical research. Nat Mater 7:758–760
Xing HY, Zhang SJ, Bu WB, Zheng XP, Wang LJ, Xiao QF et al (2014) Ultrasmall NaGdF4 nanodots for efficient MR angiography and atherosclerotic plaque imaging. Adv Mater 26:3867–3872
Xuan S, Wang F, Lai JM, Sham KW, Wang YX, Lee SF et al (2011) Synthesis of biocompatible, mesoporous Fe3O4 nano/microspheres with large surface area for magnetic resonance imaging and therapeutic applications. ACS Appl Mater Interfaces 3:237–244
Yang H, Zhuang Y, Sun Y, Dai A, Shi X, Wu D et al (2011) Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles. Biomaterials 32:4584–4593
Yang M, Gao L, Liu K, Lu C, Wang Y, Yu L et al (2015) Characterization of Fe3O4/SiO2/Gd2O(CO3)2 core/shell/shell nanoparticles as T1 and T2 dual mode MRI contrast agent. Talanta 131:661–665
Yang ZX, Qian K, Lv J, Yan WH, Liu JH, Ai JW et al (2016) Encapsulation of Fe3O4 nanoparticles into N, S co-doped graphene sheets with greatly enhanced electrochemical performance. Sci Rep 6:27957
Yang YY, Jin P, Zhang XC, Ravichandran N, Ying H, Yu CH et al (2017) New epigallocatechin gallate (EGCG) nanocomplexes co-assembled with 3-mercapto-1-hexanol and β-lactoglobulin for improvement of antitumor activity. J Biomed Nanotech 13:805–814
Yiu HH, McBain SC, Lethbridge ZAD, Lees MR, Palona I, Olariu CI et al (2011) Novel magnetite-silica nanocomposite (Fe3O4-SBA-15) particles for DNA binding and gene delivery aided by a magnet array. J Nanosci Nanotechnol 11:3586–3591
Yiu HH, Pickard MR, Olariu CI, Williams SR, Chari DM, Rosseinsky MJ (2012) Fe3O4-PEI-RITC magnetic nanoparticles with imaging and gene transfer capability: development of a tool for neural cell transplantation therapies. Pham Res 29(5):1328–1343
Zhang WZ, Liu L, Chen HM, Hu K, Delahunty I, Gao S et al (2018) Surface impact on nanoparticle-based magnetic resonance imaging contrast agents. Theranostics 8:2521–2548
Zhou Z, Huang D, Bao J, Chen Q, Liu G, Chen Z et al (2012) A synergistically enhanced T1–T2 dual-modal contrast agent. Adv Mater 24:6223–6228
Zhou X, Chen L, Wang A, Ma Y, Zhang H, Zhu Y (2015) Multifunctional fluorescent magnetic nanoparticles for lung cancer stem cells research. Colloids Surf B Biointerfaces 134:431–439
Zhou Z, Bai R, Munasinghe J, Shen Z, Nie L, Chen X (2017) T1-t2 dual-modal magnetic resonance imaging: from molecular basis to contrast agents. ACS Nano 11:5227–5232
Zielhuis SW, Seppenwoolde JH, Mateus VA, Bakker CJ, Krijger GC, Storm G et al (2006) Lanthanide-loaded liposomes for multimodality imaging and therapy. Cancer Biother Radiopharm 21:520–527
Acknowledgements
This study was financially supported the National Natural Science Foundation of China (81673438 and 51302004) and Scientific Research Foundation of the Institute for Translational Medicine of Anhui Province (SRFITMAP, 2017zhyx34).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflicts of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Fig. S1:
Raman spectra of Fe3O4@PEI@DTPA-Gd nanocomposites Fig. S2: Fluorescence images of 293 cells transfected with Fe3O4@PEI@DTPA-Gd nanocomposites carrying GFP gene b Fluorescence images of SH-SY5Y cells and HepG2 cells stained with Hoechst 33342 and PI after incubated with Fe3O4@PEI@DTPA-Gd nanocomposites for 72 h
Rights and permissions
About this article
Cite this article
Xiang, HH., Song, MM., Fei, MY. et al. Facile synthesis of multifunctional nanocomposites with good compatibility for efficient dual-mode T1 and T2 magnetic resonance imaging and gene delivery. Appl Nanosci 9, 2019–2030 (2019). https://doi.org/10.1007/s13204-019-01042-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13204-019-01042-0