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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 current study aimed to investigate the potential of methotrexate (MTX) functionalized, 5-aminolevulinic acid (5-ALA)-modified, chitosan-coated manganese dioxide (MnO 2 /CS) nanoparticles (NPs) as a targeted radiosensitizer for cancer therapy. The novelty of the current study lies in the development of the MnO 2 /CS@5-ALA-MTX NPs as a novel formulation with high encapsulation capacity, site specificity, and biosafety for targeted drug delivery. The study also emphasizes comprehensive in-vitro tests to understand the cell death mechanisms after radiosensitization. The effects of MnO 2 /CS@5-ALA-MTX NPs on U87MG cell lines treated with radiation were examined in-vitro and in-vivo. Mitochondrial function and reactive oxygen species (ROS) production were evaluated under normoxia and hypoxia conditions. The combination of MTX and 5-ALA provided tumor-targeting ability, while the CS coating prolonged the circulation time of the nano-system. The synthesized MnO 2 /CS@5-ALA-MTX NPs had an average size of 70 ± 9 nm, a Zeta potential of −6 ± 2 mV, and a polydispersity of 0.240. The loading efficiency and release profile of the drug delivery system were assessed and demonstrated its capacity for drug delivery. The MTT assay on U87MG cells revealed that MnO 2 /CS@5-ALA-MTX NPs reduced cell viability compared to MTX alone. Both in-vitro and in-vivo studies demonstrated tumor-enhanced radiosensitization using MTX functionalized MnO 2 /CS NPs. The mice receiving MnO 2 /CS@5-ALA-MTX NPs and subsequent radiation exposure exhibited significant tumor inhibition and increased survival ratios. Notably, tumor-bearing mice treated with MnO 2 /CS@5-ALA-MTX NPs and X-ray irradiation demonstrated more effective tumor rejection compared to the groups treated with X-ray alone or NPs alone. In conclusion, the results highlight the potential of MnO 2 /CS@5-ALA-MTX NPs as a targeted radiosensitizer for cancer therapy. The NPs exhibited promising tumor-inhibiting effects and enhanced radiosensitization both in-vitro and in-vivo , suggesting their potential as a valuable approach for cancer treatment in the future. [Display omitted] [ABSTRACT FROM AUTHOR]