Zhixia Li

PMMA-based bone cements containing magnetite particles for the hyperthermia of cancer

Polymethylmethacrylate-based cements containing magnetite (Fe(3)O(4)) particles were prepared and their structure and properties were investigated. The Fe(3)O(4) particles were uniformly dispersed in the cement matrix and constituted a maximum of 60 wt.% of the total weight of cement. The setting time of the cement increased and the maximum temperature during the setting reaction decreased with increasing Fe(3)O(4) content. The compressive strength of cement increased with increasing Fe(3)O(4) content. Cement with 50 wt.% Fe(3)O(4) particles generated heat in alternating magnetic fields of 300 and 120 Oe at a frequency of 100 kHz.

Preparation of Magnetic Iron Oxide Nanoparticles for Hyperthermia of Cancer in a FeCl2-NaNO3-NaOH Aqueous System

Magnetic iron oxide nanoparticles (MIONPs) were synthesized in a FeCl 2—NaNO3—NaOH aqueous system under various initial Fe2+/NO- 3 molar ratios (α) and Fe 2+/OH- molar ratios (β) in order to clarify the effects of the initial molar ratio of reactants on the reaction mechanism. The Fe 2+/NO- 3 /OH- molar ratio of 3 : 1 : 5 led to the formation of magnetic nanoparticles mainly composed of magnetite (Fe3O4) and maghemite (γ-Fe2O3). The 36 nm sized γ-Fe2O3 and 413 nm sized Fe 3O4 were obtained by changing the order in which NaNO 3 was added to a NaOH solution. The in vitro heat generations of the resulting MIONPs in an agar phantom were measured under an alternating magnetic field (100 kHz, 23.9 kA/m). The temperature rise (ΔT) of the agar phantom for the 36 nm sized γFe2O3 was 55°C in the first 140 s, with a concentration of 58 mg Fe/mL. Our results showed that it is possible to prepare MIONPs with high heating efficiencies under optimal conditions using the present method.

In vitro assessment of poly(methylmethacrylate)-based bone cement containing magnetite nanoparticles for hyperthermia treatment of bone tumor

Poly(methylmethacrylate) (PMMA)-based cements containing magnetite (C-PMMA/Fe(3)O(4)) is useful in hyperthermia treatment for bone tumor. We have prepared C-PMMA/Fe(3)O(4) by incorporating Fe(3) O(4) powders of different diameters (means of 300, 35, and 11 nm) into the polymerization reaction of methyl methacrylate monomer to develop a new bone cement with high heating efficiencies in alternating current (AC) magnetic fields. Further, we have investigated the in vitro heating capability of the cements in different AC magnetic fields. The mechanical strength and biocompatibility of the resultant cements were also assessed. Their heat generation strongly depends on the magnetite nanoparticle sizes and applied magnetic fields. The cement containing Fe(3)O(4) with mean diameter around 35 nm exhibited the highest heating capability in AC magnetic fields of 120 and 300 Oe at 100 kHz while that with mean diameter around 11 nm exhibited optimum heating capability in AC magnetic fields of 40 Oe at 600 kHz. The incorporation of Fe(3)O(4) into cement-30 wt % of the total amount of cement-did not significantly change the compressive strength of cement, and the proliferation of rat fibroblast Rat-1 cells on cement discs was not inhibited. Our investigations are useful for designing new PMMA/Fe(3)O(4) bone cement with high heating efficiencies and biocompatibilities for bone tumor treatments.

Magnetic SiO2 gel microspheres for arterial embolization hyperthermia

We have prepared magnetic SiO(2) microspheres with a diameter of 20-30 µm as thermoseeds for hyperthermia of cancer. These were prepared by directly introducing preformed magnetic iron oxide nanoparticles (IONPs) into microspheres of a SiO(2) gel matrix derived from the hydrolysis of tetramethoxysilane (TMOS) in a water-in-oil (W/O) emulsion. Dimethylformamide (DMF) was used as a stabilizer, methanol (CH(3)OH) as a dispersant and ammonia (NH(4)OH) as the catalyst for the formation of the spherical particles in the aqueous phase of the W/O emulsion. The magnetic IONPs were synthesized hydrochemically in an aqueous system composed of ferrous chloride, sodium nitrate and sodium hydroxide. Mono-dispersed magnetic SiO(2) gel microspheres with a diameter of approximately 20 µm were successfully obtained by adding a determined amount of solution with a molar ratio of TMOS/DMF/CH(3)OH/H(2)O/NH(4)OH = 1:1.4:9:20:0.03 to kerosene with a surfactant (sorbitan monooleate/sorbitan monostearate = 3:1 by weight ratio) that was 30 wt% of the total amount of the oil phase. These were estimated to contain up to 60 wt% of IONPs that consisted mainly of Fe(3)O(4) and showed a higher specific absorption rate (SAR = 27.9-43.8 W g(-1)) than that of the starting IONPs (SAR = 25.3 W g(-1)) under an alternating current magnetic field of 300 Oe and 100 kHz.

Preparation, structure, and in vitro chemical durability of yttrium phosphate microspheres for intra-arterial radiotherapy†

Chemically durable microspheres containing yttrium and/or phosphorus are useful for intra-arterial radiotherapy. In this study, we attempted to prepare yttrium phosphate (YPO₄) microspheres with high chemical durability. YPO₄ microspheres with smooth surfaces and diameters of around 25 μm were successfully obtained when gelatin droplets containing yttrium and phosphate ions were cooled and solidified in a water-in-oil emulsion and then heat-treated at 1100°C. The chemical durability of the heat-treated microspheres in a simulated body fluid at pH = 6 and 7 was high enough for clinical application of intra-arterial radiotherapy.

Adsorption characteristics of bovine serum albumin onto alumina with a specific crystalline structure

Bone cement containing alumina particles with a specific crystalline structure exhibits the ability to bond with bone. These particles (AL-P) are mainly composed of delta-type alumina (δ-Al2O3). It is likely that some of the proteins present in the body environment are adsorbed onto the cement and influence the expression of its bioactivity. However, the effect that this adsorption of proteins has on the bone-bonding mechanism of bone cement has not yet been elucidated. In this study, we investigated the characteristics of the adsorption of bovine serum albumin (BSA) onto AL-P and compared them with those of its adsorption onto hydroxyapatite (HA), which also exhibits bone-bonding ability, as well as with those of adsorption onto alpha-type alumina (α-Al2O3), which does not bond with bone. The adsorption characteristics of BSA onto AL-P were very different from those onto α-Al2O3 but quite similar to those onto HA. It is speculated that BSA is adsorbed onto AL-P and HA by interionic interactions, while it is adsorbed onto α-Al2O3 by electrostatic attraction. The results suggest that the specific adsorption of albumin onto implant materials might play a role in the expression of the bone-bonding abilities of the materials.

MC3T3-E1 and RAW264.7 cell response to hydroxyapatite and alpha-type alumina adsorbed with bovine serum albumin

Initial cell responses following implantation are important for inducing osteoconductivity. We investigated cell adhesion, spreading, and proliferation in response to native and bovine serum albumin (BSA)-adsorbed disc of hydroxyapatite (HA) or alpha-type alumina (α-Al2O3) using mouse MC3T3-E1 osteoblastic cells and mouse RAW264.7 macrophages. The adsorbed BSA inhibited adhesion and spreading of MC3T3-E1 cells, but did not affect MC3T3-E1 cell proliferation on HA and α-Al2O3 substrates. Thus, MC3T3-E1 cells quickly adhere to original HA before cell binding is impeded by adsorption of BSA in quantities sufficient to inhibit the adhesion of MC3T3-E1 cells. The adsorbed BSA inhibits adhesion of RAW264.7 cells to α-Al2O3, but not to HA. BSA adsorption does not affect RAW264.7 cell spreading and proliferation on both HA and α-Al2O3 substrates. Thus, BSA adsorbed on HA stimulates a different cell response than α-Al2O3. Moreover, quick adherence of osteoblast cells and monocyte-macrophage lineage cells plays a role in HA osteoconductivity.

In vitro apatite formation and drug loading/release of porous TiO2 microspheres prepared by sol–gel processing with different SiO2 nanoparticle contents

Bioactive titania (TiO2) microparticles can be used as drug-releasing cement fillers for the chemotherapeutic treatment of metastatic bone tumors. Porous anatase-type TiO2 microspheres around 15 μm in diameter were obtained through a sol-gel process involving a water-in-oil emulsion with 30:70 SiO2/H2O weight ratio and subsequent NaOH solution treatment. The water phase consisted of methanol, titanium tetraisopropoxide, diethanolamine, SiO2 nanoparticles, and H2O, while the oil phase consisted of kerosene, Span 80, and Span 60. The resulting microspheres had a high specific surface area of 111.7 m(2)·g(-1). Apatite with a network-like surface structure formed on the surface of the microspheres within 8 days in simulated body fluid. The good apatite-forming ability of the microspheres is attributed to their porous structure and the negative zeta potential of TiO2. The release of rhodamine B, a model for a hydrophilic drug, was rapid for the first 6 h of soaking, but diffusion-controlled thereafter. The burst release in the first 6h is problematic for clinical applications; nonetheless, the present results highlight the potential of porous TiO2 microspheres as drug-releasing cement fillers able to form apatite.

Novel Synthesis of Yttrium Phosphate Microspheres for Radioembolization of Cancer

Chemically durable microspheres containing yttrium and/or phosphorus are useful for intra-arterial radiotherapy. In the present study, we attempted to prepare yttrium phosphate (YPO4) microspheres with high chemical durability as well as smooth surface and investigated their chemical durability in simulated body environment. YPO4 microspheres with smooth surface around 25 μm were successfully obtained, when gelatin droplets containing YPO4 precursor was cooled to be solidified in water-in-oil emulsion and then heat-treated at 1100°C. The chemical durability of the heat-treated microspheres in simulated body fluid at pH =6 and 7 was high enough for clinical application of radioembolic therapy of cancer.

TiO2 microspheres containing magnetic nanoparticles for intra‐arterial hyperthermia

Magnetic microspheres measuring 15-35 µm in diameter are believed to be useful for intra-arterial hyperthermia. In this study, we attempted to prepare titanium dioxide (TiO2 ) microspheres containing magnetic nanoparticles (MNPs). MNP-containing TiO2 microspheres with diameters of approximately 30 µm were successfully obtained by sol-gel reaction of titanium tetraisopropoxide in a water-in-oil emulsion with added cosurfactant of 1-butanol and subsequent heat treatment at 200°C. The microspheres showed ferrimagnetism owing to high content of MNPs in approximately 60 wt % and had a low-crystalline TiO2 matrix. Furthermore, the agar phantom was heated to above 43°C after approximately 1 min under an alternating magnetic field of 100 kHz and 300 Oe and showed in vitro biocompatibility similar to that of MNP-free TiO2 microspheres.