Photoregulated Cross-Linking of Superparamagnetic Iron Oxide Nanoparticle (SPION) Loaded Hybrid Nanovectors with Synergistic Drug Release and Magnetic Resonance (MR) Imaging Enhancement

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• 作者：Kangning Zhu ; Zhengyu DengGuhuan Liu ; Jinming Hu ; Shiyong Liu
• 刊名：Macromolecules
• 出版年：2017
• 出版时间：February 14, 2017
• 年：2017
• 卷：50
• 期：3
• 页码：1113-1125
• 全文大小：742K
• ISSN：1520-5835

文摘

The development of stimuli-responsive magnetic resonance imaging (MRI) contrast agents that can selectively enhance imaging contrasts at pathological sites is of potential use in clinical diagnosis. Herein, a T₂-type MRI contrast agent with synergistically photoregulated enhanced MRI contrast and drug release was achieved by coassembly of superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin (DOX) with amphiphilic block copolymer assemblies. Photosensitive amphiphilic diblock copolymers, poly(ethylene oxide)-b-poly(2-((((2-nitrobenzyl)oxy)carbonyl)amino)ethyl methacrylate) (PEO-b-PNBOC), were synthesized through reversible addition–fragmentation chain transfer (RAFT) polymerizations. The resulting block copolymers were coassembled with hydrophobic oleic acid (OA)-stabilized SPIONs and DOX via an oil-in-water (O/W) emulsion and a subsequent solvent evaporation procedure, resulting in the formation of DOX/SPION coloaded hybrid nanovectors. The as-assembled hybrid nanovectors exhibited retarded DOX release and weak T₂ relaxivity (r₂) prior to UV-irradiation. However, upon UV-irradiation, the hybrid nanovectors underwent cross-linking and a hydrophobic-to-hydrophilic transition within the cores, thereby selectively triggering DOX release and elevating T₂ relaxivities. In vitro DOX release results revealed approximately 85% of DOX was released within 10 h under 20 min UV-irradiation, and this was in sharp contrast with less than 5% of DOX release without UV-irradiation. The selective DOX release under UV-irradiation showed significantly increased cytotoxicity toward HepG2 cells. Meanwhile, the r₂ of UV-irradiated nanovectors exhibited 4.5- and 1.9-fold increases as compared to cetyltrimethylammonium bromide (CTAB)-stabilized monodispersed SPIONs and nonirradiated hybrid nanovectors. Moreover, there was a linear correlation between the r₂ changes and cumulative DOX release extents, enabling instantaneously visualizing the DOX release by the MRI technique. Further, we demonstrated that the cellular internalization efficiency of the coloaded hybrid nanovectors increased by 2.7-fold in the presence of an external magnet. The magnetically guided cellular uptake, triggered release profile, and enhanced MRI contrast characteristics may presage potential applications as a new generation of theranostic platform.