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This study aimed to design and development of a magnetic natural hydrogel based on alginate (Alg), gelatin (Gel), and Fe 3 O 4 magnetic nanoparticles (MNPs) as an efficient and "smart" drug delivery system (DDS) for cancer therapy. First, Alg was partially oxidized (OAlg), and then the Alg-Gel chemical hydrogel was synthesized through "Shift-Base" condensation reaction. Afterward, Fe 3 O 4 NPs were incorporated into the hydrogel through in situ chemical co-precipitation approach. The scanning electron microscopy (SEM) image exhibited that the fabricated Alg-Gel hydrogel has porous microstructure without microphase separation. Transmission electron microscopy (TEM) revealed the well-defined formation of Fe 3 O 4 NPs throughout the Alg-Gel hydrogel with spherical shapes in the size range of 25 ± 10 nm. Saturation magnetization (δ s ) value of the Alg-Gel/Fe 3 O 4 was obtained to be 31 emu g -1 that represent proper magnetic property for "smart" drug delivery purposes. The obtained Alg-Gel/Fe 3 O 4 was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies as well as its anticancer activity was investigated against Hela cells. The formulated Alg-Gel/Fe 3 O 4 -Dox exhibited pH-dependent drug release behavior due to presence of carboxylic acid groups in the DDS. According to the results, the Alg-Gel/Fe 3 O 4 magnetic hydrogel can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)

The aim of this study was the design and development of a novel de novo drug delivery system for cancer chemotherapy. For this purpose, chitosan (CS) functionalized using phthalic anhydride followed by 4-cyano, 4-[(phenylcarbothioyl) sulfanyl] pentanoic acid as a chain transfer agent (CTA) to afford CS-CTA macroinitiator. The synthesized CS-CTA macroinitiator was then copolymerized with methacrylic acid (MAA) monomer using reversible addition-fragmentation chain transfer (RAFT) polymerization technique to produce chitosan-graft-poly(methacrylic acid) (CS-g-PMAA) graft copolymer. Afterward, graphene oxide (GO) nanosheets were incorporated into the synthesized copolymer through the physical interactions. The CS-g-PMAA/GO nanocomposite was loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The biocompatibility, DOX-loading capacity, and pH dependent drug release behavior of the developed nanocomposite were also investigated. As the experimental results, as well as superior biological and physicochemical features of CS and GO, we envision that the developed CS-g-PMAA/GO nanocomposite may be applied as de novo drug delivery nanosystem for cancer chemotherapy., (Copyright © 2018. Published by Elsevier B.V.)

This article evaluates the anticancer drug delivery performances of two nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe 3 O 4 nanoparticles. For this purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic properties of the DOX-loaded MNHGs were investigated using transmission electron microscopy (TEM) and vibrating-sample magnetometer (VSM), respectively. The sizes and zeta potentials (ξ) of the MNHGs and their corresponding DOX-loaded nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug release values at condition of 41 °C and pH 5.3. The drug-loaded MNHGs at physiological condition (pH 7.4 and 37 °C) exhibited negligible drug release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were extensively evaluated through the assessing survival rate of HeLa cells using the MTT assay, and there in vitro cellular uptake into the mentioned cell line were examined using fluorescent microscopy and fluorescence-activated cell sorting (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited higher anticancer drug delivery performance in the terms of cytotoxic effect and in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a promising de novo drug delivery system, in part due to its pH and thermal responsive drug release behavior as well as proper magnetite character toward targeted drug delivery.

The aim of this study was to synthesis and characterization of a novel stimuli-responsive polymeric nanosystem for theranostic applications. For this purpose, starch was modified by itaconic anhydride to afford an itaconat-functionalized starch macromonomer (starch-IA). This macromonomer with carboxylic functional groups was subsequently adsorbed onto the surface of iron oxide nanoparticles (Fe 3 O 4 NPs), and then copolymerized with N-isopropylacrylamide (NIPAAm) monomer via a 'free' radical initiated polymerization technique to produce a temperature-responsive magnetic nanohydrogel (MNHG). The chemical structures of all samples as representatives were characterized by means of Fourier transform infrared (FTIR) spectroscopy. The lower critical solution temperature (LCST), thermal responsibility, morphology, elemental composition, thermal stability, and magnetic properties of the synthesized MNHG were investigated. In addition, the methotrexate (MTX)-loading capacity (∼74%) and stimuli-responsive drug release ability of the synthesized MNHG were also evaluated. As results, we envision that the synthesized starch-g-PNIPAAm/Fe 3 O 4 MNHG may be find theranostic applications, in part due to its smart physicochemical properties., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A novel pH- and thermo-responsive ABC triblock copolymer {poly[(2-succinyloxyethyl methacrylate)-b-(N-isopropylacrylamide)-b-[(N-4-vinylbenzyl),N,N-diethylamine]]} [P(SEMA-b-NIPAAm-b-VEA)] was successfully synthesized via reversible addition of fragmentation chain transfer (RAFT) polymerization technique. The molecular weights of PHEMA, PNIPAAm, and PVEA segments in the synthesized triblock copolymer were calculated to be 10,670, 6140, and 9060gmol -1 , respectively, from proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. The "schizophrenic" self-assembly behavior of the synthesized P(SEMA-b-NIPAAm-b-VEA) triblock copolymer under pH and thermal stimulus were investigated by means of 1 H NMR and ultraviolet-visible (UV-vis) spectroscopies as well as dynamic light scattering (DLS) and zeta potential (ξ) measurements. The doxorubicin hydrochloride (DOX)-loading capacity, and stimuli-responsive drug release ability of the synthesized triblock copolymer were also investigated. The biocompatibility of the synthesized triblock copolymer was confirmed through the assessing survival rate of breast cancer cell line (MCF7) using MTT assay. In contrast, DOX-loaded triblock copolymer exhibited an efficient anticancer performance in comparison with free DOX verified by MTT and DAPI staining assays. As the results, we envision that the synthesized P(SEMA-b-NIPAAm-b-VEA) triblock copolymer can be applied as an enhanced anticancer drug delivery nanosystem, mainly due to its smart physicochemical and biocompatibility properties., (Copyright © 2016 Elsevier Inc. All rights reserved.)