Facile Synthesis of Gd(OH)3‐Doped Fe3O4 Nanoparticles for Dual‐Mode T1‐ and T2‐Weighted Magnetic Resonance Imaging Applications

The facile hydrothermal synthesis of polyethyleneimine (PEI)‐coated iron oxide (Fe₃O₄) nanoparticles (NPs) doped with Gd(OH)₃ (Fe₃O₄‐Gd(OH)₃‐PEI NPs) for dual mode T₁‐ and T₂‐weighted magnetic resonance (MR) imaging applications is reported. In this approach, Fe₃O₄‐Gd(OH)₃‐PEI NPs are synthesized via a hydrothermal method in the presence of branched PEI and Gd(III) ions. The PEI coating onto the particle surfaces enables further modification of poly(ethylene glycol) (PEG) in order to render the particles with good water dispersibility and improved biocompatibility. The formed Fe₃O₄‐Gd(OH)₃‐PEI‐PEG NPs have a Gd/Fe molar ratio of 0.25:1 and a mean particle size of 14.4 nm and display a relatively high r₂ (151.37 × 10^?3m ^?1 s^?1) and r₁ (5.63 × 10^?3m ^?1 s^?1) relaxivity, affording their uses as a unique contrast agent for T₁‐ and T₂‐weighted MR imaging of rat livers after mesenteric vein injection of the particles and the mouse liver after intravenous injection of the particles, respectively. The developed Fe₃O₄‐Gd(OH)₃‐PEI‐PEG NPs may hold great promise to be used as a contrast agent for dual mode T₁‐ and T₂‐weighted self‐confirmation MR imaging of different biological systems.     

Static Magnetic Field Dictates Protein Corona Formation on the Surface of Glutamine‐Modified Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) have become important tools for the imaging and detecting of prevalent diseases for many years. Scientists usually harness their attraction to a static magnetic field (SMF) to increase targeting efficiency and minimize side effects. To prolong blood circulation time and minimize reticuloendothelial system clearance, SPIONs are increasingly designed with a negatively charged surface. Understanding how a SMF affects the SPIONs with a negative surface charge is fundamental to any potential downstream applications of SPIONs as drug delivery carriers and bio‐separation nanoparticles. The goal of our study is to investigate the effect of SMF treatment (204 mT) on the in vitro and in vivo protein corona formed on negatively charged SPIONs. The results reveal that the amount of protein and the composition of protein corona is directly related to the SMF treatment. Compared with the in vivo protein corona, SMF treatment exercises considerable influence on the composition of the in vitro protein corona. The in vitro protein corona formed on SPIONs modulates the secretion of inflammatory cytokines from cells. To the best of our knowledge, this report describes the first demonstration of a SMF as an influencing factor on protein corona formation in vivo. Our results help to elucidate the biological mechanisms of SPIONs with SMF treatment and suggest that the protein corona effect should be considered during the development of a magnetic target.     

Boosting Postsurgical Outcomes of Orthotopic Hepatocellular Carcinoma via an EpCAM‐Targeting Theranostic Nanoparticle

Hepatectomy is one of the main treatments for hepatocellular carcinoma (HCC). However, because microscopic tumor residues are often present after surgery, the recurrence rate of HCC remains extremely high. A multimodality imaging‐guided multifunctional nanoparticle, indocyanine‐green–gadolinium–copper sulfide@bovine‐serum‐albumin–epithelial‐cell‐adhesion molecule (EpCAM), is developed for HCC treatment based on a novel theranostic strategy. After intravenous injection of these nanoparticles into HCC‐bearing mice, remarkably selective accumulation and highly efficient retention of the nanoparticles in tumor sites are observed. This is due to the EpCAM's specific targeting ability, which also results in enhanced HCC contrast in a tri‐modal visualization, which unites magnetic resonance, photoacoustic, and fluorescence imaging. Moreover, nanoparticle uptake into the HCC allows photothermal therapy (PTT) as an interoperative adjuvant strategy for further eliminating possible microscopic residues and boosting HCC surgery outcomes. This theranostic strategy not only helps with precise diagnosis of HCC but enables intraoperatively imaging guidance for accurate tumor resection. Moreover, postoperation longitudinal observation demonstrates that intraoperative imaging‐guided resection alongside a PTT‐integrated treatment strategy can result in a significant improvement of overall survival rate. These multifunctional EpCAM‐targeting nanoparticles may respresent a novel theranostic strategy to improve postsurgical HCC treatment.