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The purpose of this study was to analyze the encapsulation of superparamagnetic iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12-mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into living cells. The lipid nanoparticles employed in this work were highly hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the bioactive L-peptide. The particle sizes of two different magnetic lipid nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were both around 170 nm with a narrow range of size disparity. The transversal relaxivity, r2, for both LML and ML nanoparticles were found to be significantly higher than the longitudinal relaxivity r1 (r2/r1 > 20). The in vitro tumor cell targeting efficacy of the LML nanoparticles were evaluated and compared to the ML nanoparticles, upon observing cellular uptake of magnetic lipid nanoparticles by the nasopharyngeal carcinoma cells, which express cell surface specific protein for the L-peptide binding revealed. In the Prussian blue staining experiment, cells incubated with LML nanoparticles indicated much higher intracellular iron density than cells incubated with only the ML and SPION nanoparticles. In addition, the MTT assay showed the negligible cell cytotoxicity for LML, ML and SPION nanoparticles. The MR imaging studies demonstrate the better T2-weighted images for the LML-nanoparticle-loaded nasopharyngeal carcinoma cells than the ML- and SPION-loaded cells.

Superparamagnetic iron oxides nanoparticles possess specific magnetic properties to be an efficient contrast agent for magnetic resonance imaging (MRI) to enhance the detection and characterization of tissue lesions within the body. To endow specific properties to nanoparticles that can target cancer cells and prevent recognition by the reticuloendothelial system (RES), the surface of the nanoparticles was modified with folic-acid-conjugated poly(ethylene glycol) (FA-PEG). In this study, we investigated the multifunctional fluorescent magnetic nanoparticles (IOPFC) that can specifically target cancer cells and be monitored by both MRI and optical imaging. IOPFC consists of an iron oxide superparamagnetic nanoparticle conjugated with a layer of PEG, which was terminal modified with either Cypher5E or folic acid molecules. The core sizes of IOPFC nanoparticles are around 10 nm, which were visualized by transmission electron microscope (TEM). The hysteresis curves, generated with superconducting quantum interference device (SQUID) magnetometer analysis, demonstrated that IOPFC nanoparticles are superparamagnetic with insignificant hysteresis. IOPFC displays higher intracellular uptake into KB and MDA-MB-231 cells due to the over-expressed folate receptor. This result is confirmed by laser confocal scanning microscopy (LCSM) and atomic flow cytometry. Both in vitro and in vivo MRI studies show better IOPFC uptake by the KB cells (folate positive) than the HT1080 cells (folate negative) and, hence, stronger T 2-weighted signals enhancement. The in vivo fluorescent image recorded at 20 min post injection show strong fluorescence from IOPFC which can be observed around the tumor region. This multifunctional nanoparticle can assess the potential application of developing a magnetic nanoparticle system that combines tumor targeting, as well as MRI and optical imaging.

Background: MRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver‐specific contrast agents which enhance lesions in T2‐weighted images. Iron oxide nano‐particle m‐PEG‐silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial. Purpose: To evaluate the safety and clinical validity of IOP Injection as MRI contrast agent in diagnosing HCC. Study type: Prospective. Subjects: A total of 52 subjects (61.6 ± 11.05 years, 45 males/7 females) with suspected HCC. Field Strength/Sequence: 1.5 T, T1‐weighted in/opposed phase, T2*‐weighted gradient echo, T2‐weighted fast spin echo, true fast imaging with steady‐state free precession. Assessment: Adverse effects and clinical monitoring were recorded throughout the 5‐day study. Two independent readers (M.G.H. with 30 years of experience, S.P.K. with 26 years of experience) made the diagnosis. The diagnostic performance of IOP‐enhanced MRI was evaluated with sensitivity and positive predictive value by comparing to the pathology reports from subsequent hepatic resection. The number of lesions with various sizes and degrees of differentiation detected by IOP‐enhanced MRI was assessed. The relative change in signal intensities over time was indirectly measured from acquired images. Statistical Tests: Sensitivity and positive predictive value were used to evaluate the diagnostic performance of IOP‐enhanced MRI. Prevalence‐adjusted and bias‐adjusted 휅 coefficient was used to assess the interreader variability. Results: No serious adverse event related to IOP Injection was found. IOP Injection enhanced the lesion‐to‐liver contrast ratio in T2*‐weighted images by 50.1% ± 4.8%. IOP‐enhanced MRI detected HCC with 100% sensitivity by subject and 96% sensitivity by lesion. IOP Injection visualized subtle vascular invasion as filling defect within vessels in true fast imaging with steady‐state free precession (TrueFISP) images. Data Conclusion: IOP Injection was safe and efficacious as MRI contrast agent in diagnosing HCC in a limited group of subjects. Evidence Level: 2. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]