781861b3611b8fa779c02338b09b3e7a pmc_34361181.pdf 7c607d51de87c4cf62d03e9f6ee8231224fa427d pmc_34361181.pdf fbfe49a52bccbec6a1b3f4b3b31bad38ae6d2e4c74755f105238b8b418aaa911 pmc_34361181.pdf Title: Hydrotalcite-Embedded Magnetite Nanoparticles for Hyperthermia-Triggered Chemotherapy Subject: A magnetic nanocomposite, consisting of Fe3O4 nanoparticles embedded into a Mg/Al layered double hydroxide (LDH) matrix, was developed for cancer multimodal therapy, based on the combination of local magnetic hyperthermia and thermally induced drug delivery. The synthesis procedure involves the sequential hydrolysis of iron salts (Fe2+, Fe3+) and Mg2+/Al3+ nitrates in a carbonate-rich mild alkaline environment followed by the loading of 5-fluorouracil, an anionic anticancer drug, in the interlayer LDH space. Magnetite nanoparticles with a diameter around 30 nm, dispersed in water, constitute the hyperthermia-active phase able to generate a specific loss of power of around 500 W/g-Fe in an alternating current (AC) magnetic field of 24 kA/m and 300 kHz as determined by AC magnetometry and calorimetric measurements. Heat transfer was found to trigger a very rapid release of drug which reached 80% of the loaded mass within 10 min exposure to the applied field. The potential of the Fe3O4/LDH nanocomposites as cancer treatment agents with minimum side-effects, owing to the exclusive presence of inorganic phases, was validated by cell internalization and toxicity assays. Keywords: layered double hydroxide; Fe3O4; continuous flow synthesis; magnetic hyperthermia; nanocomposite; drug delivery; cell internalization Author: Konstantinos Simeonidis, Efthimia Kaprara, Pilar Rivera-Gil, Ruixue Xu, Francisco J. Teran, Evgenios Kokkinos, Athanassios Mitropoulos, Nikolaos Maniotis and Lluis Balcells Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 20 12:38:06 2021 CEST ModDate: Tue Jul 20 12:45:35 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 27860792 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OPZDHV+VnURWPalladioL Type 1 Custom yes yes no 10 0 CHOLVW+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 GYRDZE+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 FFCOJD+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 NPLVPL+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 54 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 58 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 62 0 HISNTR+CMSY10 Type 1 Builtin yes yes no 74 0 JHYTSG+CMR10 Type 1 Builtin yes yes no 103 0 DVTUXA+EURM10 Type 1 Builtin yes yes no 110 0 IBMJPA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 124 0 IBMJPB+PalatinoLinotype CID TrueType Identity-H yes yes yes 127 0 IBMKAC+PalatinoLinotype TrueType WinAnsi yes yes no 133 0 IBMKAE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 136 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-09-11 02:56:10 CEST RepresentationInformation: pmc_34361181.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-08-16 03:35:30 CEST Size: 27860792 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 354 FreeObjects: 17 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Nanocomposite Synthesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Magnetic Heat Losses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Drug Loading and Release Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Cell Internalization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Toxicity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Results and discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Material Properties Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Hyperthermia Performance Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Drug Release Behavior Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Cellular Uptake and Biocompatibility Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: Hydrotalcite-Embedded Magnetite Nanoparticles for Hyperthermia-Triggered Chemotherapy Author: Konstantinos Simeonidis, Efthimia Kaprara, Pilar Rivera-Gil, Ruixue Xu, Francisco J. Teran, Evgenios Kokkinos, Athanassios Mitropoulos, Nikolaos Maniotis and Lluis Balcells Subject: A magnetic nanocomposite, consisting of Fe3O4 nanoparticles embedded into a Mg/Al layered double hydroxide (LDH) matrix, was developed for cancer multimodal therapy, based on the combination of local magnetic hyperthermia and thermally induced drug delivery. The synthesis procedure involves the sequential hydrolysis of iron salts (Fe2+, Fe3+) and Mg2+/Al3+ nitrates in a carbonate-rich mild alkaline environment followed by the loading of 5-fluorouracil, an anionic anticancer drug, in the interlayer LDH space. Magnetite nanoparticles with a diameter around 30 nm, dispersed in water, constitute the hyperthermia-active phase able to generate a specific loss of power of around 500 W/g-Fe in an alternating current (AC) magnetic field of 24 kA/m and 300 kHz as determined by AC magnetometry and calorimetric measurements. Heat transfer was found to trigger a very rapid release of drug which reached 80% of the loaded mass within 10 min exposure to the applied field. The potential of the Fe3O4/LDH nanocomposites as cancer treatment agents with minimum side-effects, owing to the exclusive presence of inorganic phases, was validated by cell internalization and toxicity assays. Keywords: layered double hydroxide; Fe3O4; continuous flow synthesis; magnetic hyperthermia; nanocomposite; drug delivery; cell internalization Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 20 12:38:06 CEST 2021 ModDate: Tue Jul 20 12:45:35 CEST 2021 ID: 0x83d9869ff2dcb5e99cc138cfa2eb4535, 0x83d9869ff2dcb5e99cc138cfa2eb4535 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: GYRDZE+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: GYRDZE+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JHYTSG+CMR10 FontSubset: true FirstChar: 61 LastChar: 61 FontDescriptor: FontName: JHYTSG+CMR10 Flags: Symbolic FontBBox: -40, -250, 1009, 750 FontFile: true Font: BaseFont: FFCOJD+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: FFCOJD+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 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