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A dual stimuli-responsive magnetic nanohydrogel was fabricated as a potent drug delivery system (DDS) for 'smart' treatment of cancer by chemo/hyperthermia approach. For this objective, Fe 3 O 4 nanoparticles (NPs) were produced via a co-precipitation approach and then modified by 3-(trimethoxysilyl) propylmethacrylate (MPS) moiety. The modified NPs were copolymerized with N , N '-(dimethylamino)ethyl methacrylate (DMAEMA), and maleic anhydride (MA) monomers by a free radical polymerization approach to afford a Fe 3 O 4 @P(DMAEMA- co -MA) core-shell NPs. Afterward, the NPs were shell crosslinked by the reaction of anhydride unites with neutralized cystamine (Cys). The fabricated pH- and reduction-responsive magnetic nanohydrogel was physically loaded with methotrexate (MTX), as an anticancer drug, and its drug loading efficiency (LE) was calculated as 64 ± 2.7%. The developed nanohydrogel/MTX exhibited proper stimuli-triggered drug release behavior that qualified it as an efficient DDS according to the abnormal micro-environment of cancerous tumors. The anticancer activity investigation using chemo/hyperthermia therapy approach by MTT-assay revealed that the nanohydrogel/MTX might show better clinical outcomes than those of the free MTX.

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly( N -isopropylacrylamide- block -acrylic acid) (HS-PNIPAAm- b -PAA) onto Fe 3 O 4 @Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe 3 O 4 @Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm- b -PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe 3 O 4 @Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe 3 O 4 @Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe 3 O 4 @Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe 3 O 4 nanomaterials in its structure.

Nanoparticles are ubiquitous in the environment and are widely used in medical science (e.g. bioimaging, diagnosis, and drug therapy delivery). Due to unique physicochemical properties, they are able to cross many barriers, which is not possible for traditional drugs. Nevertheless, exposure to NPs and their following interactions with organelles and macromolecules can result in negative effects on cells, especially, they can induce cytotoxicity, epigenicity, genotoxicity, and cell death. Lipid-based nanomaterials (LNPs) are one of the most important achievements in drug delivery mainly due to their superior physicochemical and biological characteristics, particularly its safety. Although they are considered as the completely safe nanocarriers in biomedicine, the lipid composition, the surfactant, emulsifier, and stabilizer used in the LNP preparation, and surface electrical charge are important factors that might influence the toxicity of LNPs. According to the author's opinion, their toxicity profile should be evaluated case-by-case regarding the intended applications. Since there is a lack of all-inclusive review on the various aspects of LNPs with an emphasis on toxicological profiles including cyto-genotoxiciy, this comprehensive and critical review is outlined.

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.