Tóm tắt Luận án Synthesis and properties of ferrite - Metal (Ag, Au) hybrid nanostructures for biomedical application

2.1. Fe3O4/Ag hybrid NPs Fe3O4/Ag hybrid NPs were synthesized by seeded-growth method (Fe3O4 NPs were used as seeds) in the ODE solvent. The reactions were carried out with  = [Ag]/[Fe] in the range of 0.5 ÷ 13.6. The effect of temperature on the hybrid structure was investigated. 2.2.2.2. Fe3O4/Au hybrid NPs a) Fe3O4/Au hybrid NPs The synthesis of Fe3O4/Au NPs was similar to that of Fe3O4/Ag nanoparticles (section 2.2.2.1) but H[AuCl4].3H2O was used instead of AgNO3. b) Hollow Fe3O4/Au hybrid NPs The hollow Fe3O4/Au hybrid NPs were synthesized by the Galvanic replacement method and Fe3O4/Ag nanoparticles (section 2.2.2.1) were used as a template. The effect of the amount of the H[AuCl4] solution on the formation of the hollow Fe3O4/Au structure was investigated. 2.2.3. Phase transfer nanoparticles into water After synthesized, NPs were transferred phase into water using PMAO. 2.3. Material characterization 2.3.1. Transmission electron microscopy 6 2.3.2. X-ray diffraction 2.3.3. Vibrating sample magnetometer 2.3.4. Molecular absorption spectroscopy UV-Vis 2.3.5. Fourier Transform Infrared Spectroscopy 2.3.6. Energy Dispersive X-Ray Spectroscopy 2.3.7. Thermal gravimetric analysis 2.3.8. Dynamic light scattering 2.4. Methods of evaluating the toxicity of materials The toxicity of hybrid nanomaterials on AGS and MKN45 cells was evaluated by MTT method. 2.5. Methods of evaluating antibacterial activity of materials The evaluation of the antibacterial activity of materials was carried out by the agar well diffusion method. Bacterial species tested: Gram-positive bacteria: Bacillus subtilis (B. subtilis), Lactobacillus plantarum (L.plantarum), Sarcina lutea (S. lutea). + Gram-negative bacteria: Serratia marcescens (S. marcescens), Escherichia coli (E. coli). 2.6. Determination of the magneto-photothermal conversion efficiency The magnetic/photo induced heating efficiency of materials was carried out under three conditions: (i) Magnetic hyperthermia (MHT) at the magnetic field with an intensity of 100 - 300 Oe and frequency of 450 kHz, (ii) Photothermial therapy (PTT) at 808 nm laser, a power density of 0.2 – 0.65 W/cm2, and (iii) combined magnetic field and laser at the exact same conditions (MHT + PTT). 2.7. Magnetic resonance imaging MRI images of different material concentrations were taken on a Siemens magnetic resonance device (Model: MAGNETOM Avanto 1.5 T) with an alternating magnetic field (64 MHz and 1.5 tesla). 7 CHAPTER 3. RESULTS AND DISCUSSION 3.1. Magnetic ferrite nanoparticles 3.1.1. Morphology 3.1.1.1. Synthesis of Fe3O4 NPs at low concentration of precursors Normally, Fe3O4 NPs were synthesized by thermal decomposition in dibenzyl ether, a toxic organic solvent. In this thesis, 1-octadecene, a solvent with much lower toxicity level, was tested and used as a solvent. The effect of several factors such as time, reaction temperature, surfactant concentration, and inorganic precursor concentration on Fe3O4 nanoparticle size was determined by TEM and the results are presented in Table 3.1. Table 3.1. Effect of reaction conditions on Fe3O4 nanoparticle size. Precursor concentration (mM) Surfactant concentration (mM) Tempe rature (oC) Time (min) Samples dTEM (nm) Fe(acac)3 FeSO4. 7H2O FeCl2. 4H2O OA OLA 190 0 0 372 372 295 30 F1 3.6 ± 0.7 60 F2 4.5 ± 0.7 120 F3 7.2 ± 1.0 190 0 0 558 558 295 10 F4 3.2 ± 0.5 30 F5 4.1 ± 0.6 60 F6 6.3 ± 0.9 120 F7 10.7 ± 1.4 190 0 0 744 744 295 10 F8 3.4 ± 0.5 30 F9 6.7 ± 0.7 60 F10 8.1 ± 0.7 120 F11 13.9 ± 1.1 190 0 0 930 930 295 10 F12 5.8 ± 0.9 30 F13 11.3 ± 1.2 60 F14 14.7 ± 1.3 126.7 0 63.3 558 558 270 60 F15 4.8 ± 1.0 295 F16 8.4 ± 1.5 315 F17 10.2 ± 0.5 126.7 63.3 0 558 558 315 F18 10.8 ± 2.4 8 a) Effect of reaction time Figure 3.1. TEM images of the samples F8 (a), F9 (b), F10 (c), F11 (d) and corresponding particle size distribution histograms (e) All the Fe3O4 NPs are spherical, monodisperse, and uniform in size. When the reaction time increases from 10 ÷ 120 minutes, the particle size increases and is in the range of 3.2 ÷ 14.7 nm. b) Effect of surfactant concentration Figure 3.2. TEM images of the samples F2 (a), F6 (b), F10 (c) and F14 (d) and corresponding particle size distribution histograms (e) The obtained particles are spherical, uniform, and monodisperse, and the average particle size increases as the concentration of OA and OLA increases. c) Effect of inorganic precursors In order to reduce the cost and widen the applications, Fe(acac)3 was partly replaced by inorganic Fe(II) salts which are much cheaper than Fe(acac)3. 9 Figure 3.3. TEM images and corresponding particle size distribution histograms of samples F17 (a, b) and F18 (c, d) Of the two inorganic salts, FeCl2 gave uniform Fe3O4 NPs which were similar to those formed when only Fe(acac)3 was used. d) Effect of reaction temperature At 270 o C and 295 o C, the obtained Fe3O4 NPs are not uniform, and particle boundaries are not clear. At 315 o C (boiling point of the solvent), the average size of Fe3O4 particles is 10.2 ± 0.5 nm, the particles are uniformly distributed, and their boundaries are clearer. Figure 3.4. TEM images of samples F15 (a), F16 (b), F17 (c) and corresponding particle size distribution histograms (d). 3.1.1.2. Synthesis of magnetic ferrite NPs at high precursor concentration Hình 3.5. TEM images of Fe3O4 NPs (a1, a2), CoFe2O4 NPs (b1, b2) and MnFe2O4 NPs (c1, c2) synthesized at high precursor concentration. The magnetic ferrite particles synthesized at the high precursor concentration are still uniform and monodisperse. 3.1.2. Crystalline structure The as-synthesized materials have characteristic peaks corresponding to the (220), (311), (222), (400), (422), (511) và (440) planes in the ferrite spinel structure. 10 3.1.3. Magnetic properties When the particle size of Fe3O4 increases 3.2 ÷ 14.7 nm, the saturation magnetization (Ms) value rises 40.0 ÷ 66.5 emu/g and the coercivity (Hc) increases 0 ÷ 57 Oe. For the samples with particle size  10 nm, Hc is below 6 Oe. On the other hand, with the same particle size, the Ms value of magnetic ferrites decreases in the order of CoFe2O4, Fe3O4, and MnFe2O4. 3.1.4. Structure of the shell coating magnetic ferrite NPs The FT-IR spectra of magnetic ferrite samples have relatively similar absorption peaks, which characterize the vibrations of bonds in surfactants (OA/OLA). According to the TGA curve, the real mass of the magnetic core is about 90% Summary of results section 3.1: 1. Magnetic ferrite nanoparticles MFe2O4 (M: Fe, Co, Mn) were successfully fabricated by thermal decomposition in ODE solvent. The obtained NPs are highly uniform and monodisperse and have a spinel structure. By varying the synthesis conditions (time, reaction temperature, surfactant concentration, and precursor concentration), the particle size in the range of 3.2 ÷ 14.7 nm can be controlled. With the partial replacement of Fe(acac)3 by FeCl2 and at a high concentration of precursors, the magnetic ferrite particles are still highly uniform and monodisperse. 2. The value of the magnetic saturation of Fe3O4 NPs increases from 40.0 to 66.5 emu/g when the particle size increases from 3.2 to 14.7 nm. At room temperature, the obtained material has a very small coercivity and can be considered as superparamagnetic, that meets the requirements for biomedical applications. 3. Magnetic ferrite nanoparticles MFe2O4 are coated with a surfactant layer (OA/OLA) with a mass 10%. 3.2. Fe3O4-(Ag, Au) hybrid NPs According to the study of synthesis of the magnetic ferrite NPs, four Fe3O4 samples with different particle size: 6.7 ± 0,7 nm (F9), 8.1 ± 0.7 nm (F10), 10.2 ± 0.5 nm (F17) và 13.9 ± 1.1 nm (F11) were selected as the seeds for synthesizing Fe3O4-(Ag, Au) NPs. 3.2.1. Morphology 3.2.1.1. Fe3O4/Ag hybrid NPs Fe3O4/Ag hybrid NPs were synthesized by the seeded-growth method in ODE solvent. The parameters: [Ag]/[Fe] ratio and reaction time affecting the structure of Fe3O4/Ag are given in Table 3.5. 11 Table 3.5. Effect of synthetic conditions on Fe3O4/Ag hybrid structure  = [Ag]/[Fe] Reaction time Fe3O4/Ag hybrid structure 0.5 30 Core - shell 60 Core - shell 1.4 30 Core - shell 60 Core - shell 2.3 30 Core - shell 60 Core - shell 3.2 30 Core - shell 60 Core - shell 4.5 30 Core - shell 60 Core - shell 120 Core - shell 6.8 30 Core - shell 60 Core - shell 120 Core - shell 9.0 30 Dumbbell, Core - shell 60 Dumbbell, Core - shell 120 Dumbbell, Core - shell 11.4 30 Dumbbell 60 Dumbbell 120 Dumbbell 13.6 30 Dumbbell 60 Dumbbell 120 Dumbbell a) Effect of molar ratio between precursor and seed ([Ag]/[Fe]) Figure 3.10. TEM images (a - g) and corresponding particle size distribution histograms (h) of Fe3O4 (seeds) and Fe3O4/Ag hybrid NPs with the variation of  = [Ag]/[Fe] 12 When  is below 6.8, the obtained hybrid NPs have shell-core structure. When this value is increased to 9, the dumbbell structure is formed. Thus, when the value of  = [Ag]/[Fe] increases, the morphology of Fe3O4/Ag hybrid NPs changes from core-shell to the dumbbell. b) Effect of reaction time When the reaction time is 30 and 60 minutes, the particles are relatively uniform. As the reaction time is extended to 120 minutes the agglomeration of two or more nanoparticles occurs. This trend is similar to that in the case of using Fe3O4 seeds with different sizes. Figure 3.12. TEM images of Fe3O4/Ag hybrid structure synthesized with different reaction time: a1, b1) 30 min, a2, b2) 60 min, (a3, b3) 120 min. The size of the Ag shell in the core-shell structure and the Ag particles in the dumbbell structure increase as the reaction time increases. From the above analysis results, we can summarize the diagram describing the formation of Fe3O4/Ag hybrid structure as shown in Figure 3.13. Figure 3.13. Diagram describing the morphological development of Fe3O4/Ag hybrid structure 13 3.2.1.2. Fe3O4/Au hybrid NPs a) Fe3O4/Au NPs The Fe3O4/Au core-shell NPs were synthesized with [Au]/[Fe] molar ratio of 6.8. b) Hollow Fe3O4/Au hybrid NPs The hollow Fe3O4/Au hybrid NPs were synthesized by using Fe3O4@Ag (core-shell) NPs as the template via Galvanic replacement reaction between Ag and Au 3+ in ODE solvent: 3Ag 0 + Au 3+  Au0 + 3Ag+ *) Effect of Fe3O4@Ag template on the formation of hollow Fe3O4/Au structure: When Fe3O4@Ag template is 12.8 nm, hollow Fe3O4/Au structure is not formed. As the template is 16.0 nm, the small holes in the middle of the hybrid NPs can be observed on TEM image, and the obtained solution has a characteristic blue color, demonstrating the formation of the hollow Fe3O4/Au hybrid NPs. Figure 3.15. TEM images and corresponding solutions of Fe3O4@Ag template (a1, a2) and Fe3O4/Au hybrid NPs (b1, b2) Thus, the formation of hollow Fe3O4/Au hybrid NPs depends on the Fe3O4@Ag template and the proposed mechanism is given in Figure 3.16. Figure 3.16. Diagram describing the formation mechanism of hollow Fe3O4/Au hybrid nanostructure 14 *) Effect of the amount of H[AuCl4] solution on the formation of hollow Fe3O4/Au hybrid structure When the volume of H[AuCl4] solution used in the reaction is 0.5 mL, the hollow structure is not formed. For larger amounts of H[AuCl4] (from 1.0 to 2.0 mL), the particles are converted into cage like structures, and the void size gradually increased. At 2.0 mL, the largest size of material reaches 17.0 nm. Further increasing the volume of H[AuCl4], the hollow spheres are gradually broken, and at 3.5 mL, the hollow structure is completely ruined. Figure 3.17. TEM images of Fe3O4@Ag NPs (a), Fe3O4/Au NPs (b-i) at different amounts of H[AuCl4] solution and particle size distribution histograms (k) of (a and e). The development of Fe3O4/Au hybrid structure morphology depends on the amount of H[AuCl4] solution used. This relationship can be summarized according to Figure 3.18. Figure 3.18. Effect of amounts of H[AuCl4] solution on the morphology of Fe3O4/Au hybrid structure. 15 Figure 3.19. XRD patterns of Fe3O4, Ag and Fe3O4/Ag NPs 3.2.2. Crystalline structure On the XRD pattern of Fe3O4@Ag core-shell structure, only characteristic peaks of Ag cubic structure can be observed while XRD data of Fe3O4-Ag dumbbell structure shows typical peaks of both Fe3O4 spinel (low intensity) and Ag (high intensity). 3.2.3. Optical properties In the wavelength range from 300 - 900 nm, Fe3O4 NPs do not have absorption peaks. Ag NPs have an SPR peak at 405 nm, Fe3O4/Ag hybrid NPs have SPR peaks at 410 nm with the core-shell structure (sample F10@A60, 16.0 nm) and 420 nm with dumbbell structure (sample F10-A60, 8.1-16.3 nm). In general, the SPR peak of Fe3O4/Ag hybrid nanoparticles is below 450 nm. Figure 3.20. UV-Vis spectra of NPs in n-hexane solvent: a) Fe3O4, Ag and Fe3O4/Ag NPs, b) Fe3O4 and Fe3O4/Au NPs. The optical properties of Fe3O4/Au hybrid NPs depend on the morphology and structure of the materials. Fe3O4/Au hybrid NPs have an SPR peak at 530 nm, while hollow Fe3O4/Au hybrid NPs have an SPR peak at 707 nm (the sample with 2 mL of Au 3+ ). The SPR position of the hollow Fe3O4/Au hybrid NPs depends on the amount of H[AuCl4] solution (Table 3.10). Table 3.10. Effect of the amounts of H[AuCl4] solution on the SPR position of Fe3O4/Au hybrid NPs. H[AuCl4] (mL) 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 The SPR position of Fe3O4/Au (nm) 410 587 627 645 707 592 585 565 16 3.2.4. Magnetic property The values of saturation magnetization and coercivity of Fe3O4/Ag hybrid samples are lower than pure magnetic NPs, but the magnetic response of hybrid NPs is relatively good. Figure 3.21. a) The magnetization curves of Fe3O4 and Fe3O4/Ag NPs; b) Photographs of Fe3O4/Ag NPs in n-hexane without and with magnet Figure 3.22. The magnetization curves of Fe3O4@Ag template and Fe3O4/Au NPs and image (inset) of hollow Fe3O4/Au hybrid NPs in n-hexane without and with magnet. The formation of hollow Fe3O4/Au structure does not change the superparamagnetic properties when compared to that of Fe3O4@Ag template, but the value of saturation magnetization increases slightly (Figure 3.22). 3.2.5. Chemical composition The composition of Fe3O4/Ag hybrid NPs consists of the main elements Fe, Ag and O, and that of Fe3O4/Au, includes Fe, Ag, Au and O. According to SEM-EDS elemental mapping analysis, Fe3O4/Au hollow NPs (the sample with 2 mL of Au 3+ ) show the good distribution of all elements in the hollow nanostructure (Figure 3.25). Summary of results of section 3.2: 1. Fe3O4/Ag hybrid NPs were successfully fabricated by the seeded-growth method in ODE solvent and their morphology can be controlled by varying  = [Ag]/[Fe] and reaction time. With   6.8, the particles have Fe3O4@Ag core-shell structure, while with  = 9 Fe3O4-Ag dumbbell structure is formed. The size of the Ag shell in the Figure 3.25. SEM-EDS elemental mapping of hollow Fe3O4/Au hybrid NPs. 17 core-shell structure and the Ag particles in the dumbbell structure increase as the reaction time increases. 2. The hollow Fe3O4/Au hybrid NPs were fabricated by using Fe3O4/Ag NPs as the template via Galvanic replacement reaction between Ag and Au 3+ . The obtained material has an average size of 17 nm and its SPR peak can be controlled to 707 nm. With [Au]/[Ag] = 0.83, Fe3O4/Au hybrid NPs have the largest void size, and all elements are well distributed. 3. The as-synthesized Fe3O4-(Ag, Au) NPs have superparamagnetic properties at room temperature with the value of the saturation magnetization in the range of 7 ÷ 27 emu/g, lower than that of the Fe3O4 seed samples (50 ÷ 64 emu/g). 3.3. Nanoparticles are coated by PMAO 3.3.1. Phase transfer of nanoparticles by PMAO Before being coated with PMAO, the hybrid NPs are dispersible in n-hexane and after coated, they are well-dispersed in water (Figure 3.26). Figure 3.26. Phase transfer of the NPs by PMAO (a), solutions of Fe3O4@Ag NPs (b), Fe3O4-Ag NPs (c) and hollow Fe3O4/Au NPs (d) before (1) and after phase transfer (2). 3.3.2. Optical properties of materials Figure 3.27. Solution (a) and UV-Vis spectra (b) of Fe3O4@Ag@PMAO and hollow Fe3O4/Au@PMAO NPs at different amounts of Au 3+ . 18 The change in color of the hybrid NPs solutions is also shown by the shift of the SPR peak of the materials (Figure 3.27). Among the solutions of Fe3O4/Au hybrid NPs coated by PMAO, the 2.0 mL Au 3+ sample has the strongest SPR peak shifting to the near-infrared region. This sample was selected for further studies. 3.3.3. Structure of the coating shell FT - IR spectra confirm that the hybrid NPs were coated with PMAO. TGA curves indicate that PMAO shell accounts for 58% and Fe3O4/Au hybrid NPs make up 42% of the sample mass. Figure 3.28. FT-IR spectra of hollow Fe3O4/Au hybrid NPs before and after phase tranfer Hình 3.29. TGA curves of hollow Fe3O4/Au hybrid NPs before and after phase tranfer The hydrodynamic diameters determined by DLS of Fe3O4@Ag@PMAO and hollow Fe3O4/Au@PMAO are 25.85 and 28.84 nm, respectively. Zeta potential of Fe3O4@Ag@PMAO and hollow Fe3O4/Au@PMAO aqueous solutions is -42.5 mV and -40.0 mV, respectively. Moreover, hybrid NPs are stable in NaCl solution at concentration of 150 ÷ 250 mM and pH of 2 ÷ 11. These results demonstrate that the solution of the hybrid NPs is well dispersed and stable under the investigated conditions. 3.3.5. Toxicity evaluations of materials The toxicity of the solutions of Fe3O4@Ag@PMAO and hollow Fe3O4/Au@PMAO hybrid NPs was evaluated on two gastric cancer cell lines AGS and MKN45 by MTT method. *) Fe3O4@Ag hybrid NPs: At Fe3O4@Ag@PMAO concentration below 20 µg/mL, AGS and MKN45 cells grew normally, similar to those of the control sample. At higher sample concentrations (20 ÷ 100 µg/mL), the morphology and nuclei of the cells were altered. The IC50 values determined for AGS and MKN45 cell lines are 42 µg/mL and 58 µg/mL, respectively. 19 Figure 3.33. The growth rate of AGS (a) and MKN45 (b) cells after treated in 48 h with Fe3O4@Ag@PMAO hybrid NPs. Figure 3.34 . Morphology (a) and neuclei (b) of AGS cells after treated in 48 h with Fe3O4@Ag@PMAO hybrid NPs. Figure 3.35. Morphology (a) and neuclei (b) of MKN45 cells after treated in 48 h with Fe3O4@Ag@PMAO hybrid NPs. *) Fe3O4/Au hollow hybrid nanoparticles: Hollow Fe3O4/Au@PMAO hybrid NPs is non-toxic on AGS and MKN45 cells within the test concentration range of 10 ÷ 100 g/mL. Figure 3.36. The growth rate of AGS (a) and MKN45 (b) cells after treated in 48 h with hollow Fe3O4/Au@PMAO hybrid NPs. 20 Figure 3.37. Morphology (a) and neuclei (b) of AGS cells after treated in 48 h with hollow Fe3O4/Au@PMAO hybrid NPs. Figure 3.38. Morphology (a) and neuclei (b) of MKN45 cells after treated in 48 h with hollow Fe3O4/Au@PMAO hybrid NPs. Summary of the results of section 3.3: 1. Hybrid NPs were successfully transferred into the water by PMAO, and the optical properties of the materials remain unchanged. The SPR peaks of hollow Fe3O4/Au@PMAO hybrid NPs are in the NIR region and can shift to 707 nm. The hybrid NPs after the phase transfer are well dispersed and stable in water for 12 months, the their Zeta potential values were over 37 mV. The Fe3O4@Ag@PMAO and hollow Fe3O4/Au@PMAO hybrid NPs are stable in the solution with salt concentration of 150 ÷ 250 mM and pH of 2 ÷ 11. 2. Fe3O4@Ag@PMAO hybrid NPs exhibits toxicity to AGS and MKN45 cells, depending on the material concentration. The IC50 values determined for AGS and MKN45 cells are 42 µg/mL and 58 µg/mL, respectively. The hollow Fe3O4/Au@PMAO hybrid NPs does not show toxicity on AGS and MKN45 cells in the range of 10 ÷ 100 g/mL. 3.4. Applicability of hybrid nanomaterials in biomedicine + Study on the antibacterial activity of the solution of Fe3O4/Ag@PMAO hybrid NPs with two structures: Fe3O4@Ag@PMAO core-shell (sample F10@A60@PMAO) and Fe3O4-Ag@PMAO dumbbell (sample F10-A60@PMAO) and compare with Fe3O4@PMAO (sample F10@PMAO) and Ag@PMAO. + Study on the magneto-photothermal conversion efficiency and MRI image contrast of hollow Fe3O4/Au@PMAO hybrid NPs (the sample 2 mL Au 3+ ). 21 3.4.1. Antibacterial activity of the materials Fe3O4@PMAO Ag@PMAO Fe3O4@Ag@PMAO Fe3O4-Ag@PMAO Figure 3.39. Antibacterial activity of Fe3O4@PMAO, Ag@PMAO and Fe3O4/Ag@PMAO hybrid NPs. Ag@PMAO NPs solution can inhibit the growth of bacteria, but the inhibition zones are not clear with all tested bacteria. The Fe3O4@PMAO NPs (seeds) have no antibacterial effect, however, when they combine with silver to form Fe3O4/Ag@PMAO hybrid structure, the antibacterial activity is clearly enhanced. 3.4.2. The magneto-photothermal conversion efficiency of the materials 3.4.2.1. The magnetic heating (MHT) Figure 3.40a shows a significantly dependent behavior of magnetic field for the final attained temperature after 1200 s of treatment, and they tend to increase as the magnetic intensity increases. The maximum value of SLP ~ 310 W/g is achieved under the applied magnetic field of 300 Oe at a frequency of 450 kHz. In order to reach the therapeutic temperature window (42 ÷ 46 o C), a magnetic field with a minimum intensity of 150 Oe is required. 22 Figure 3.40. Magnetic hyperthermia: (a) Temperature elevation profile for the hollow Fe3O4/Au @PMAO hybrid NPs under different magnetic fields at a constant frequency, f = 450 kHz (a) and the corresponding SLP value (b) 3.4.2.2. The plasmonic heating (PTT) Figure 3.41. Photothermal therapy: Heating curves for the hollow Fe3O4/Au @PMAO hybrid NPs under irradiation with a 808 nm laser for values of the different power densities (a) and corresponding SLP values (b) When the laser power at a density of 0.2 ÷ 0.35 W/cm 2 is applied, the highest temperature is reached below 40 o C after 1200 s. To reach the therapeutic temperature window, a minimum power density of P = 0.50 W/cm 2 is required. When the laser power density increases from 0.2 to 0.65 W/cm 2 , the SLP value increases from 152.70 to 1074.62 W/g. 3.4.2.3. The magneto-plasmonic heating (MHT + PTT) The rate of heating of (MHT + PTT) and PTT is faster than that of MHT: the temperature variation (T) after 300 s of the dual heating method (MHT + PTT) is 36 o C, 6 times larger than that of MHT (6 o C), and that of PTT (21 o C) is larger than that of MHT about 3.5 times. After 1200 s of treatment, the temperature varies significantly under all experimental conditions. The highest temperature achieved by the three modes of heating MHT, PTT, and (MHT + PTT) is 52.0, 55.0 and 68.5 o C, respectively, corresponding to the temperature variation T of 38.5, 25.0 and 22.0 oC. The control sample (distilled water) shows a very low-temperature rise (1.0 ÷ 2.5 o C) for all three experimental modes. 23 Figure 3.42. Heating curve (a) and SLP value (b) for the hollow Fe3O4/Au @PMAO hybrid NPs and H2O under combining magnetic field and laser. *) Effect of magnetic field intensity (H) Figure 3.43. The magneto-plasmonic heating (MHT + PTT) of hollow Fe3O4/Au@PMAO hybrid NPs under different magnetic fields (a), corresponding SLP value of a (b), the maximum temperature elevation Tmax (after 1200 s) ( c) and the corresponding SLP value (d) under MHT and (MHT + PTT). When the magnetic field intensity (H) increases from 100 to 250 Oe, the highest temperature (Tmax) increases from 47 to 68 o C. To achieve therapeutic temperatures with the MHT method, a minimum magnetic field intensity of 150 Oe is required, while for the technique (MHT + PTT) it is 100 Oe (at a laser with P = 0.5 W/cm 2 ). Thus, by combining two heating methods (MHT + PTT), the magnetic field intensity has been reduced by 1.5 times compared to the case where only MHT is applied and the therapeutic temperature is still reached. * Effect of laser power density (P): When the power density (P) increases from 0.2 to 0.65 W/cm 2 , the obtained Tmax increases from 46 to 68.5 o C. The maximum SLP value obtained in this case is 1082.75 W/g with P = 0.65 W/cm 2 . In order to 24 reach the target temperature window by using PTT technique, a minim