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A novel theranostic nanoplatform was prepared based on Fe 3 O 4 nanoparticles (NPs) coated with gadolinium ions decorated-polycyclodextrin (PCD) layer (Fe 3 O 4 @PCD-Gd) and employed for Curcumin (CUR) loading. The dissolution profile of CUR indicated a pH sensitive release manner. Fe 3 O 4 @PCD-Gd NPs exhibited no significant toxicity against both normal and cancerous cell lines (MCF 10A and 4T1, respectively); while the CUR-free NPs showed more toxicity against 4T1 than MCF 10A cells. In vivo anticancer study revealed appropriate capability of the system in tumor shrinking with no tissue toxicity and adverse effect on body weight. In vivo MR imaging of BALB/c mouse showed both T 1 and T 2 contrast enhancement on the tumor cells. Fe 3 O 4 @PCD-Gd/CUR NPs showed significant features as a promising multifunctional system having appropriate T 1 -T 2 dual contrast enhancement and therapeutic efficacy in cancer theranostics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

β -Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic system (Gd 2 O 3 @PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd 2 O 3 @PCD-FA was fully characterised by FTIR, vibrating sample magnetometer, TGA, XRD, SEM and TEM analyses. The dissolution profile of DOX showed a pH sensitive release. No significant toxicity was observed for the targeted NPs (Gd 2 O 3 @PCD-FA) and DOX-loaded NPs inhibiting M109 cells viability more efficiently than free DOX. Moreover, the negligible hemolytic activity of the targeted NPs showed their appropriate hemocompatibility. The preferential uptake was observed for the developed Gd 2 O 3 @PCD-FA-DOX NPs in comparison with Dotarem using T 1 - and T 2 -weighted MRI in the presence of folate receptor-positive and folate receptor-negative cancer cells (M109 and 4T1, respectively). Furthermore, in vivo studies revealed that Gd 2 O 3 @PCD-FA-DOX not only exhibited considerably relaxivity performance as a contrast agent for MRI, but also improved in vivo anti-tumour efficacy of the system. The results suggest that Gd 2 O 3 @PCD-FA-DOX improves its therapeutic efficacy in the treatment of solid tumours and also reduces the adverse effects, so it could be proposed as a promising drug delivery system for chemotherapy and molecular imaging diagnosis in MRI.

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.

Objectives: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). Materials and methods: The developed Gd2O3@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 Gd2O3@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 Gd2O3@PCD–FA NPs enable targeted contrast T1- and T2-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 Gd2O3@PCD–FA up to 5.89 ± 1.3 within 1 h under T1-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 Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. Conclusion: The results indicate the potential of Gd2O3@PCD–FA to serve as a novel targeted nano-contrast agent in MRI. [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]