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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.)

Super Paramagnetic Iron Oxide Nanoparticles have attracted much attention in drug delivery systems because of their considerable surface-to-volume ratio and content as well. In this regard, in this study, four different formulations of magnetic nanoparticles were synthesized via various polymeric coating layer (beta-cyclodextrin, Chitosan, Gum Arabic, and Alginate) in order to find an appropriate polymer in terms of higher drug loading efficiency and capacity. Molecular dynamics simulation and Quantum mechanics were manipulated to examine the interaction mechanism between the polysaccharide polymers and Doxorubicin. Based on the calculated results, As the best candidate, bCD was chosen for DOX loading. DOX, a hydrophilic drug, was loaded into each of the four formulations. The optimum formulation, Fe3O4-ßCD, possessed loading efficiency and capacity, with 97% and 13%, respectively. The selected nanocarrier was fully characterized by Fourier Transform Infrared, VSM, TGA, XRD, SEM, UV-Vis, DLS, and TEM. TEM result exhibited the prepared Fe3O4-ßCD-DOX nanoparticles had a spherical shape (core and shell) and the size of around 15 nm. In vitro release investigation was conducted using HPLC analysis in the phosphate-buffered saline in acidic (pH=5.4) and neutral (pH=7.4) medium. The obtained results demonstrated that a sustain release performance for more than 72 h with the amount of 50% DOX release in pH=5.4. Cytotoxicity assay showed the toxicity of bare Fe3O4 and Fe3O4-ßCDNPsagainst MDA-MB468 cancerous cell and MCF10A normal cell was negligible and DOX-loaded NPs (Fe3O4-ßCD-DOX) illustrated a higher toxicity in MDA-MB468 cancerous cells than MCF 10A normal cells. The results showed that Fe3O4-ßCD-DOXNPs could improve the therapeutic efficacy and also reduce the adversarial effects; accordingly, the prepared system could be served as a promising drug delivery system in cancer treatment. [ABSTRACT FROM AUTHOR]

The combination of imaging contrast media and treatment strategies in one nanosystem has received great attention for cancer detection and treatment. This study aimed to develop Au@MnO/PEG/5FU (AMP/5FU) nanoparticles (NPs) for dual-modal CT/MRI and 5-Fluorouracil (5FU) anticancer drug delivery. The NPs showed a high 5FU loading capacity (90%), pH-responsive release profile, considerable X-ray attenuation, and MRI r1 relaxivity of 4.36 mM−1s−1. They had a significant toxic impact against A549 cancer cells that was greater than that of free 5FU. AMP/5FU NPs can be considered as a high potential multifunctional nanosystem for dual-modal CT/MRI and pH-responsive 5FU delivery. [ABSTRACT FROM AUTHOR]

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]

Objective: A novel efficient pH-sensitive targeted magnetic resonance imaging (MRI) contrast agent and innovative radio-sensitizing system were synthesized based on MnO2 NPs coated with biocompatible poly-dimethyl-amino-ethyl methacrylate-Co-itaconic acid, (DMAEMA-Co-IA) and targeted with methotrexate (MTX). Materials and methods: The as-established NPs were fully characterized and evaluated for MRI signal enhancement, relaxivity, in vitro cell targeting, cell toxicity, blood compatibility, and radiotherapy (RT) efficacy. Results: The targeted NPs MnO2@Poly(DMAEMA-Co-IA) and MTX-loaded NPs inhibited MCF-7 cell viability more effectively than free MTX after 24 and 48 h, respectively, with no noticeable toxicity. Additionally, the insignificant hemolytic activity demonstrated their proper hemo-compatibility. T1-weighted magnetic resonance imaging was used to distinguish the differential uptake of the produced MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in malignant cells compared to normal ones in the presence of high and low MTX receptor cells (MCF-7 and MCF-10A, respectively). In MRI, the produced theranostic NPs displayed pH-responsive contrast enhancement. As shown by in vitro assays, treatment of cells with MnO2@Poly(DMAEMA-Co-IA)-MTX NPs prior to radiotherapy in hypoxic conditions significantly enhanced therapeutic efficacy. Conclusion: We draw the conclusion that using MnO2@Poly(DMAEMA-Co-IA)-MTX NPs in MR imaging and combination radiotherapy may be a successful method for imaging and radiation therapy of hypoxia cells. [ABSTRACT FROM AUTHOR]

A novel targeted tumor contrast agent in magnetic resonance imaging (MRI) was synthesized based on Fe3O4@Au nanoparticle coated with polyethylene glycol (PEG) and decorated with trastuzumab (TZ). The prepared system was fully characterized, and relaxivity, cytotoxicity, colloidal stability, blood compatibility, in vitro cell targeting ability, cytotoxicity, and in vivo MR contrast enhancement were evaluated. The developed system with a size of about 30 nm exhibited excellent stability, blood compatibility, proper relaxivity, negligible in vitro cytotoxicity, and suitable in vivo negative contrast enhancement. Appropriate negative signal enhancement in MRI confirmed the efficiency of the system to be suggested as an encouraging candidate for accurate cancer diagnosis. [ABSTRACT FROM AUTHOR]

Contrast agents (CAs) play a critical role in high-resolution magnetic resonance imaging (MRI) applications to enhance the low intrinsic sensitivity of MRI. Manganese oxide nanoparticles (MnO) have gotten developing consideration as substitute spin-lattice (T1) MRI CAs as a result of the Gd-based CAs which are related with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide NPs. In this review, previous developments in the usage of MnO nanoparticles as MRI CAs for cancer theranostic applications such as developments in toxicological properties, distribution and tumor microenvironment (TME)-responsive biomaterials were reviewed. A literature search was accomplished to discover distributed research that elaborates the use of MnO in multimodal imaging and therapy. In the current study, the electronic search including PubMed/Medline, Embase, ProQuest, Scopus, Cochrane and Google Scholar was performed dependent on Mesh key words. CAs can significantly improve the imaging contrast among the lesions and normal tissues. In this study we generally concentrate on typical advancements of MnO nanoparticles about properties, bimodal or multimodal imaging, and therapy. Numerous researches have demonstrated MnO-based nanostructure produce considerable biocompatibility with the lack of cytotoxicity. Therefore, remarkable features improved photothermal therapy, chemotherapy and Chemodynamic therapy. [ABSTRACT FROM AUTHOR]

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 (Gd2O3@PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd2O3@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 (Gd2O3@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 Gd2O3@PCD-FA-DOX NPs in comparison with Dotarem using T1- and T2-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 Gd2O3@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 Gd2O3@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. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) have shown a great potential as a novel contrast agent in magnetic resonance imaging (MRI) due to their unique properties including versatile structures, composition, and surface chemistry. Fe-MIL-88B-NH2 (MILs) was synthesized using Fe+3 ions and 2-aminoterephthalic acids (NH2-BDC) in the presence of acetic acid and Pluronic F127 under a hydrothermal process. Three MILs in different sizes were synthesized by using variant CH3COOH/Fe+3 molar ratios and denoted as MIL-S, MIL-M, and MIL-L having average sizes of 60, 350, and 730 nm, respectively. The effect of aspect ratio and particle size of MILs was investigated on proton relaxivity and contrast enhancement in aqueous, in vitro, and in vivo MR images. MRI study indicated that by increasing the MILs size, the incremental transverse relaxivity was achieved from 13.53 to 50.80 for r2 and from 38.75 to 60.25 for r2*, while the difference between r2 and r2* was decreased obviously. The r2/r1 ratios were found to be 5.80, 42.27, and 127.00 for MIL-S, MIL-M, and MIL-L, respectively. All MILs demonstrated T2-weighted MR imaging performance. Furthermore, no susceptibility artifacts were observed on T2-weighted images of MILs. By decreasing the size of MILs, r2/r1 ratio was reduced sharply and T1 contrast was also observed for MIL-S. MIL-S was used for in vitro and in vivo study due to its capability in simultaneous T1 and T2 contrast enhancements. MTT and hemolysis assays showed no significant cytotoxicity and hemolysis for MIL-S against normal human breast cell line (MCF-10A) and red blood cells, respectively, at concentrations of Fe+3 up to 300 μg/mL (p < 0.05). T1-weighted images acquired from in vitro study interestingly showed that the signal intensity of MIL-S is more than Dotarem. The in vivo experiment revealed that the signal intensity of mice liver decreased sharply after injection resulting in increase of negative contrast enhancement. The negative contrast enhancement decreased gradually by the time under T2-weighted imaging mode confirming application of MIL-S as a T2 contrast agent in biomedical applications (up to 12 h post-injection). Although a decrease of the size resulted in bright contrast in aqueous solution for MIL-S, it did not show proper efficiency for in vivo positive contrast enhancement. The advantages, including simple preparation and accessibility, acceptable potency and selectivity, blood compatibility, and suitable cytocompatibility as well as enough circulation time, make MIL-S as a dual MRI contrast agent to differentiate between low-contrast tissues for in vivo experiments. [ABSTRACT FROM AUTHOR]

• A novel theranostic nano-system was designed based on Magnetite decorated with Gd3+ ions. • Novel polycyclodextrin was prepared for Gd3+ ions chelation and curcumin delivery. • The target system showed more toxicity against 4T1 than MCF 10A cells. • In vivo anti-tumor study confirmed capability of the system in tumor shrinking without body weight changes. • In vitro and in vivo analysis showed efficacy of the system for T 1 -T 2 dual modality MR imaging. 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. [ABSTRACT FROM AUTHOR]