Recent advances in superparamagnetic iron oxide nanoparticles for cellular imaging and targeted therapy research

Abstract

Advances of nanotechnology have led to the development of nanomaterials with both potential diagnostic and therapeutic applications. Among them, superparamagnetic iron oxide (SPIO) nanoparticles have received particular attention. Over the past decade, various SPIOs with unique physicochemical and biological properties have been designed by modifying the particle structure, size and coating. This article reviews the recent advances in preparing SPIOs with novel properties, the way these physicochemical properties of SPIOs influence their interaction with cells, and the development of SPIOs in liver and lymph nodes magnetic resonance imaging (MRI) contrast. Cellular uptake of SPIO can be exploited in a variety of potential clinical applications, including stem cell and inflammation cell tracking and intra-cellular drug delivery to cancerous cells which offers higher intra-cellular concentration. When SPIOs are used as carrier vehicle, additional advantages can be achieved including magnetic targeting and hyperthermia options, as well as monitoring with MRI. Other potential applications of SPIO include magnetofection and gene delivery, targeted retention of labeled stem cells, sentinel lymph nodes mapping, and magnetic force targeting and cell orientation for tissue engineering.

Fig. (1)

TEM images of the Fe₃O₄ particles synthesized by using different volume ratios of ethylene glycol to diethylene glycol. (a) 20/0, 300 nm; (b) 10/10, 165 nm; (c) 5/15, 90 nm; and (d) 1/19, 18 nm (reproduced with permission from reference 34).

Fig. (2)

Intracellular iron content in L929, RAW 264.7, HepG2, PC-3, U-87 MG, and primary cultured mouse MSCs after 24 hours incubation of SPIO nanoparticles with iron concentration at 4.5 µg/mL. Note: Data were expressed as means ± standard deviations from three experiments. Abbreviations: MSC, mesenchymal stem cell; SPIO@SiO2-NH2, aminosilane-coated SPIO nanoparticles; SPIO@SiO2, SiO2-coated SPIO nanoparticles; SPIO@dextran, dextran-coated SPIO nanoparticles (reproduced with permission from reference 85).

Fig. (3)

Optical microscopy images of the rabbit MSCs with Prussian blue staining, demonstrating the SPIO@SiO2-NH2 nanoparticle distribution within mesenchymal stem cells (original magnification: 200×). A) Image showing close to 100‰ labeling efficiency. B) Image showing numerous SPIO nanoparticles in four MSCs (reproduced with permission from reference 86).

Fig. (4)

One 0.8-cm hepatocellular carcinoma was found in the liver of a 63-year-old man. A. Neither the arterial-phase CT image (left) nor the portal venous-phase CT image (right) reveals the presence of a lesion. B. SPIO-enhanced respiratory-triggered T2-weighted turbo spin-echo image (left) and breath-hold T2*-weighted fast image obtained with steady state precession (right) depict the tumor as an area of high signal intensity (arrows). The tumor was surgically confirmed (reproduced with permission from reference 102).

Fig. (5)

This figure shows that how small lymph nodes supposed to be benign due to their size can be malignant. Images on the left hand are pre-contrast images, while the post-sinerem images on the right show hypersignal intensity small lymph nodes, which is a sign of malignancies. MRI at 3T allows a perfect depiction of these small lesions with high spatial resolution (Courtesy of Prof. Dr. Jelle Barentsz, Prostate MR-Center of Excellence, Afdeling Radiologie, Radboud Universiteit Nijmegen Medisch Centrum, the Netherlands).

Fig. (6)

A: pH-dependant SPIO nanoshell dissolution in endosomes/ lysosomes mimicking acidic buffers. 50 μg/ml SPIO nanoshells were incubated with 20 mM citrate buffer at pH 4.5, 5.0, 5.5 or PBS at pH 7.4. The dissolution rate was calculated by measuring the iron concentration of the supernatants. B & C: TEM images of U-87 MG cells after incubation with 5 mg ml^-1 SPIO nanoshells for 24 h. Intracellular SPIO nanoshells are distributed in the endosomal/lysosomal compartments, but not in the nucleus and other supermicrostructures, and a fraction of nanoshells is disintegrated (reproduced from reference 145 with permission).

Fig. (7)

U-87 MG cells were incubated with 5 μg/ml SPIO nanoparticles for 24 h. Cells were subsequently stained with 1 μM LysoSensor™ Green DND-189 (green) and 100 ng/ml Hoechst 33342 (blue) for 30 min, and then observed by the fluorescent microscope. The merged images of phase contrast, LysoSensor green and Hoechst 33342 staining indicate the co-localization of endosomes/lysosomes and SPIO nanoshells. Scale bar = 25 μm. Intracellular delivery of hydrophobic anticancer drugs by hollow structured SPIO facilitated intracellular curcumin delivery and also enhanced cytotoxic effect for doxorubicin (DOX) (reproduced from reference 145 with permission). (The color version of the figure is available in the electronic copy of the article).

Fig. (8)

Schematic diagram of hollow SPIO nanoshell based chemoembolization composites for transcatheter anticancer drug delivery. Step 1: synthesis of hollow SPIO nanoshells; Step 2: encapsulation of anti-cancer drug into the SPIO nanoshells; Step 3: formation of anti-cancer drug filled SPIO nanoshells with PVA to become 0.5~1mm chemoembolization composites; Step 4: chemoembolization composites delivered through a catheter to embolize the arteries supplying blood to the tumor; Step 5: After a period of time, chemoembolization composite dissembled and SPIO nanoshell passed through the leaky tumor vasculature into the tumor tissue, and the anti-tumor drugs were released within the tumor (reproduced with permission from reference 159).

Fig. (9)

A: SPIO embolization particles containing nanoshell/doxorubicin/PVA composites B: Composite embolization particles being passed through a catheter for selective hepatic artery drug delivery.

Fig. (10)

TEM image (Left) and Energy-dispersive X-ray spectroscopy spectrum (Right) of the SPIO@C nanoparticle (reproduced with permission from reference 182).