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

Abstract

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 T 2 -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 asassembled hybrid nanovectors exhibited retarded DOX release and weak T 2 relaxivity (r 2 ) 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 T 2 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 r 2 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 r 2 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.

SPIONs/DOX loaded polymer nanoparticles for MRI detection and efficient cell targeting drug delivery

“…[5][6][7][8][9] Increasing efforts are devoted to preparing biostable and biocompatible SPIONs in aqueous media with functional polymeric coatings to avoid these disadvantages. [10][11][12] Conventionally, to stabilize magnetic nanoparticles for medical applications, SPIONs were incorporated into crosslinked polymers to form magnetic nanocomposites due to the excellent watersolubility and colloidal stability of crosslinked polymers, [13][14][15][16] which processed a phase transfer reaction based on exchanging surface surfactants on SPIONs with amphiphilic molecules, such as PEG, 17 dextran, 18 or PEI. 19 However, the drug release will be prevented due to an excessively stabilized or nondegradable crosslinked polymer structure at aimed tissue or cell, and the nanoparticles will accumulate in the normal cells causing a long-term toxicity, thus reducing the theranostic efficiency.…”

Clustering of Iron Oxide Nanoparticles with Amphiphilic Invertible Polymer Enhances Uptake and Release of Drugs and MRI Properties

“…Their hydrophobic fragments are intended to interact with hydrophobic NPs, while hydrophilic constituents allow for water dispersibility and biocompatibility. Amphiphilic copolymers have been actively utilized for iron oxide NP functionalization, in particular, to develop drug delivery vehicles …”

Evaluation of non-targeting, C- or N-pH (low) insertion peptide modified superparamagnetic iron oxide nanoclusters for selective MRI of liver tumors and their potential toxicity in cirrhosis

“…[9][10][11][12][13] Furthermore, SPIO has been widely used in diagnosis and therapy of other cancers such as prostate cancer diagnosis and drug delivery. [14][15][16][17][18][19] On the other hand, the potential cytotoxicity of SPIO has recently been considered as a major safety concern, [19][20][21] especially in chronic liver diseases due to SPIO induced iron overload resulting in increased risks of steatohepatitis and cirrhosis progression and liver lesions in obesity. [22][23][24][25][26] One way to enhance the safety prole of SPIO was to utilize the target-specic delivery strategy such as cRGD ligand or pH (low) insertion peptide (pHLIP).…”