Search

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]

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. [ABSTRACT FROM AUTHOR]

In this study, we developed a nanoparticle system for drug delivery across the blood–brain barrier (BBB). The nanoparticle consisting of loperamide and poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer were prepared by the nanoprecipitation method; then the nanoparticles were coated with poloxamer 188 or polysorbate 80. The effects of poloxamer 188 or polysorbate 80 on the physicochemical and pharmaceutical properties of the coated nanoparticles were investigated. Loperamide, which does not cross the blood–brain barrier (BBB) but exerts antinociceptive effects after direct injection into the brain, was encapsulated by different polymeric materials and used as a model drug. The in vitro BBB penetration study shows that the surfactant-coated PLGA-PEG-PLGA nanoparticles could have penetration of 14.4–21.2%, which was better than the PLGA-PEG-PLGA nanoparticles (PEP) (8.2%) and the PLGA nanoparticles (PN) (4.3%). The biopsy studies also confirm that the PEP coated by surfactant could increase the penetration. The results of nanoparticles accumulation in brain tissue show that the PEP coated by surfactant had a much higher concentration than both the PEP and the PN. Moreover, the maximal possible antinociception effect (MPE) for the surfactant-coated PEP was 21–35% at 150 min after administering the drug intravenously, which was significantly better than just the PEP (MPE: 11.6%). The results of the formalin test show that the surfactant-coated PEP administered intravenously 150 min prior to the formalin injection could greatly reduce the pain response in the first phase. The results demonstrate that the surfactant-coated PEP could help to deliver loperamide across the BBB. [ABSTRACT FROM AUTHOR]

In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.