Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MR imaging.
We report a polyethyleneimine (PEI)-mediated approach to synthesizing hyaluronic acid (HA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo targeted tumor magnetic resonance (MR) imaging applications. In this work, Fe3O4 NPs stabilized by PEI were first synthesized via a one-pot hydrothermal method. The formed PEI-stabilized Fe3O4 NPs were then modified with fluorescein isothiocyanate (FI) and HA with two different molecular weights to obtain two different Fe3O4 NPs (Fe3O4-PEI-FI-HA6K and Fe3O4-PEI-FI-HA31K NPs) with a size of 15-16 nm. The formed HA-modified multifunctional Fe3O4 NPs were characterized via different techniques. We show that the multifunctional Fe3O4 NPs are water-dispersible and colloidal stable in different aqueous media. In vitro cell viability and hemolysis studies reveal that the particles are quite cytocompatible and hemocompatible in the given concentration range. Furthermore, confocal microscopy and flow cytometry data demonstrate that HA-targeted Fe3O4 NPs are able to be uptaken specifically by cancer cells overexpressing CD44 receptors, and be used as efficient probes for targeted MR imaging of cancer cells in vitro and xenografted tumor models in vivo. With the tunable amine-based conjugation chemistry, the PEI-stabilized Fe3O4 NPs may be functionalized with other biological ligands or drugs for diagnosis and therapy of different biological systems.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, PR China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
Jingchao
J
Li
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai 201600, PR China.
Yao
Y
He
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
Wenjie
W
Sun
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
Yu
Y
Luo
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, PR China.
Hongdong
H
Cai
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
Yunqi
Y
Pan
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China. Electronic address: mwshen@dhu.edu.cn.
Mingwu
M
Shen
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai 201600, PR China. Electronic address: xiajd_21@163.com.
Jindong
J
Xia
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, PR China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China. Electronic address: xshi@dhu.edu.cn.
Xiangyang
X
Shi
D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival; D005290:Ferric Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D005434:Flow Cytometry; D005453:Fluorescence; D006461:Hemolysis; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010316:Particle Size; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry; D013696:Temperature; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D005290:Ferric Compounds; D014867:Water; C000499:ferric oxide; D011094:Polyethyleneimine; D006820:Hyaluronic Acid
Hyaluronic acid; Iron oxide nanoparticles; MR imaging; Polyethyleneimine; Targeting; Tumors