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This study introduces a simple method for preparing a new generation of MnO 2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO 2 NMs, flower-like M1-MnO 2 and near-spherical M2-MnO 2 , were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (M s ), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO 2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO 2 . Furthermore, the signal intensity and r 1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO 2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T 1 MRI contrast activities could be employed as a promising theranostic system for future purposes., (© 2023. Springer Nature Limited.)

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (Fe 3 O 4 /CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (Fe 3 O 4 /CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (Fe 3 O 4 /CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free Fe 3 O 4 /CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded Fe 3 O 4 /CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). Fe 3 O 4 /CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T 2 MR signal intensity for Fe 3 O 4 /CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the Fe 3 O 4 /CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T 2 MRI contrast efficiency., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd 2 O 3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA)., Materials and Methods: The developed Gd 2 O 3 @PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement., Results: In vitro cytotoxicity and hemolysis assays revealed that Gd 2 O 3 @PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd +3 /mL and have high blood compatibility at concentration of up to 500 µg Gd +3 /mL. In vitro MR imaging experiments showed that Gd 2 O 3 @PCD-FA NPs enable targeted contrast T 1 - and T 2 -weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd 2 O 3 @PCD-FA up to 5.89 ± 1.3 within 1 h under T 1 -weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd 2 O 3 @PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h., Conclusion: The results indicate the potential of Gd 2 O 3 @PCD-FA to serve as a novel targeted nano-contrast agent in MRI.

This study introduces a simple method for preparing a new generation of MnO2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO2 NMs, flower-like M1-MnO2 and near-spherical M2-MnO2, were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (Ms), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO2. Furthermore, the signal intensity and r1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T1 MRI contrast activities could be employed as a promising theranostic system for future purposes. [ABSTRACT FROM AUTHOR]

• A dual cellular and metabolic T 1 and T 2 * contrast agent was formulated. • CS-modified Gd 2 O 3 NPs were applied for 5-ALA delivery. • CS-coated Gd 2 O 3 NPs improved significantly transverse and longitudinal relaxivities. • 5-ALA combined with FAC improved remarkably the transverse relaxation rate of C 6 cells treated with the NPs. Diagnosis of glioblastoma multiforme (GBM) with high sensitivity and specificity requires cellular and metabolic imaging. In this study, we aimed to endow gadolinium oxide nanoparticles (Gd 2 O 3 NPs) as an interesting T 1 contrast agent with T 2 * contrast ability through intracellular iron assistance induced by 5-aminolevulinic acid (5-ALA) with ferric ammonium citrate (FAC). Chitosan (CS)-loaded Gd 2 O 3 NPs were loaded with 5-aminolevulinic acid (Gd 2 O 3 /CS-TPP@5-ALA NPs), and then evaluated as a pH-responsive dual cellular and metabolic T 1 and T 2 * contrast agent for GBM diagnosis. The target NPs with an average size of 138 nm revealed concentration-dependent toxicity against glioblastoma C 6 cells. The relaxation rate (R 1) of the C 6 cells treated with Gd 2 O 3 /CS-TPP@5-ALA NPs plus FAC was remarkably higher than the controls including Gd 2 O 3 /CS-TPP NPs, Gd 2 O 3 /CS-TPP@5-ALA NPs, and FAC (17.2 ± 2.4 vs. 8 ± 1.5, 8.4 ± 1.2, and 2.3 ± 0.5, respectively). Interestingly, the transverse relaxation rate (R 2 *) of the C 6 cells treated with Gd 2 O 3 /CS-TPP@5-ALA NPs + FAC was significantly higher than the controls including Gd 2 O 3 /CS-TPP NPs, Gd 2 O 3 /CS-TPP@5-ALA NPs, and FAC (96 ± 8 vs. 25 ± 4, 27 ± 5, and 19 ± 2.6, respectively). We believe that Gd 2 O 3 /CS-TPP@5-ALA NPs + FAC could be introduced as promising dual cellular and metabolic T 1 -T 2 * contrast agents for GBM diagnosis in MRI. [ABSTRACT FROM AUTHOR]