Tumor size dependent MNP dose evaluation in realistic breast tumor models for effective magnetic hyperthermia.

The goal of the current investigation is to determine the breast tumor size-dependent MNP (Magnetic nano-particle) dose (mg/cm3) that can induce the required therapeutic effects during magnetic nanoparticle hyperthermia (MNH). The investigation is done through the MNH simulations on the tumor models generated from DCE_MRI DICOM images of breast cancer from TCIA ('The Cancer Imaging Archive'). Five tumor models are created from MRI data using 3D slicer software having size range of 3 cm3 to 15 cm3. The FEM-based solver (COMSOL multi-physics) is used to simulate bioheat transfer physics in all five extracted models. Single and multi-point injection strategies have been adopted to induce MNP in tumor tissues. The required MNP dose that may induce necessary therapeutic effects is evaluated by comparing the therapeutic effects produced by constant dose (CD) (5 mg/cm3) and variable reduced dose (RD) (5.5-2.8 mg/cm3) methodologies. Results show that for the requisite therapeutic effects, injected MNP doses (mg/cm3) should not remain constant as the size of the tumor increases. In fact, MNP dose  (mg/cm3) should be reduced as the size of the tumor increases. Results also show that RD works better with a multi-injection strategy than a single injection of MNP. It has been found that the effective MNP dose  (mg/cm3) is reduced by 50 % for the biggest tumor size (15 cm3) using multi-injection MNP delivery with respect to the smallest tumor (3 cm3) selected in this study.

Mild magnetic hyperthermia is synergistic with an antibiotic treatment against dual species biofilms consisting of S. aureus and P. aeruginosa by enhancing metabolic activity.

OBJECTIVE: The wound biofilm infections that develop tolerance to standard-of-care antimicrobial treatment has been increasing. The objective of this study was to demonstrate a proof-of-concept of mild magnetic nanoparticle (MNP)/alternating magnetic field (AMF) hyperthermia as an anti-biofilm therapy against multispecies biofilm infections. METHODS: Using both an in vitro cell culture and in vivo murine model of wound infection, we investigated whether MNP/AMF hyperthermia applied at a mild thermal dosage would be synergistically effective against dual species biofilm infection consisting of S. aureus and P. aeruginosa when combined with a broad-spectrum antibiotic, ciprofloxacin (CIP). RESULTS: The combined treatment of MNP/AMF hyperthermia and CIP to the wounds of diabetic mice (db/db mice) significantly reduced the CFU number of S. aureus and P. aeruginosa by 2-log and 3-log, respectively, compared to the untreated control group, whereas either mild MNP/AMF hyperthermia or CIP treatment alone had little effect on the eradication of both bacteria. Our gene microarray data obtained from the culture of S. aureus biofilm suggest that mild MNP/AMF could shift the expression of genes for cellular respiration from anaerobic fermentation to an aerobic glycolytic/tricarboxylic acid cycle (TCA) pathway, implicating that the beneficial effect of mild MNP/AMF hyperthermia on the increased susceptibility of biofilm bacteria to an antibiotic treatment is associated with an increased metabolic activity. CONCLUSION: Our results support the translational potential of mild MNP/AMF as an adjunctive therapy that can be combined with a broad-spectrum antibiotic treatment for the management of wound biofilm infections associated with multispecies bacteria.

Effects of injection rates and tissue diffusivity in magnetic nano-particle hyperthermia.

Effects of injection rate and tumor physiology on the diffusion of magnetic nano-particles (MNPs) and temperature profile during magnetic hyperthermia are investigated in this work. The study considers three injection rates (2.5 µL/min, 10 µL/min, and 40 µL/min), and two MNP diffusion coefficients (10-9 m2/s and 10-11 m2/s). The simulation of this physics has been done on 3D tumor surrounded by healthy tissue. Transient MNP distribution in tissue is evaluated using Darcy's flow model and the MNP transport (convection-diffusion) equation. The temperature profile in the tumor model is computed by solving Penne's bioheat transfer equation (PBHTE). Results show tumors with high collagen content (with low MNP diffusivity) are more restrictive towards MNP transport than tumors having low collagen content. Thus, tumors with low MNP diffusivity need a higher injection rate to increase the homogeneity of MNP concentration as well as temperature profile during thermo-therapy. Results also show that, MNP fluid injected with a higher injection rate produces a more uniform MNP concentration up to greater depth than the lower injection rate.

Screening for α-glucosidase inhibitors from Selaginella uncinata based on the ligand fishing combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry.

Biflavonoids are naturally occurring compounds consisting of two flavonoid moieties that have received substantial attention from researchers. Although many kinds of biflavonoids are typically distributed in Selaginella uncinata with hypoglycemic effect, their anti-α-glucosidase activities are not yet clear. In this study, a ligand fishing strategy for fast screening of α-glucosidase inhibitors from S. uncinata was proposed. α-Glucosidase was first immobilized on Fe3 O4 magnetic nanoparticles (MNPs) and then the α-glucosidase-functionalized MNPs were incubated with crude extracts of S. uncinata to fish out the ligands. Furthermore, considering the similarity and easy confusion of the structures of biflavonoids, the fragmentation patterns of different types of biflavonoids were studied. Based on this, 11 biflavonoids ligands with α-glucosidase inhibitory activities were accurately and quickly identified from S. uncinata with ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry. Furthermore, these ligands were confirmed to be potential inhibitors through the in vitro inhibitory assay and molecular docking.

Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma.

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors.

Magnetic Hydrogel Composite for Wastewater Treatment.

Nanocomposite hydrogels are highly porous colloidal structures with a high adsorption capacity, making them promising materials for wastewater treatment. In particular, magnetic nanoparticle (MNP) incorporated hydrogels are an excellent adsorbent for aquatic pollutants. An added advantage is that, with the application of an external magnetic field, magnetic hydrogels can be collected back from the wastewater system. However, magnetic hydrogels are quite brittle and structurally unstable under compact conditions such as in fixed-bed adsorption columns. To address this issue, this study demonstrates a unique hydrogel composite bead structure, providing a good adsorption capacity and superior compressive stress tolerance due to the presence of hollow cores within the beads. The gel beads contain alginate polymer as the matrix and MNP-decorated cellulose nanofibres (CNF) as the reinforcing agent. The MNPs within the gel provide active adsorption functionality, while CNF provide a good stress transfer phenomenon when the beads are under compressive stress. Their adsorption performance is evaluated in a red mud solution for pollutant adsorption. Composite gel beads have shown high performance in adsorbing metal (aluminium, potassium, selenium, sodium, and vanadium) and non-metal (sulphur) contaminations. This novel hybrid hydrogel could be a promising alternative to the conventionally used toxic adsorbent, providing environmentally friendly operational benefits.

CT/MR detectable magnetic microspheres for self-regulating temperature hyperthermia and transcatheter arterial chemoembolization.

The embolic microspheres containing magnetic nanoparticles and anti-tumor drugs have been proposed for transcatheter arterial chemoembolization (TACE). However, this technique still suffers the poor control of hyperthermia temperature and drug release behavior. Herein, the magnetic microspheres based on low Curie temperature superparamagnetic iron oxide nanoparticles are developed by emulsification cross-linking of gelatin, genipin, and sodium alginate. The magnetic microspheres can self-regulate the hyperthermia temperature at around 50°C, un-necessitating any temperature control facilities. The magnetic microspheres can load doxorubicin hydrochloride and the loaded drug can be released in a controllable way by using an alternating magnetic field. Cytocompatibility and hemolysis evaluations confirm the non-cytotoxicity and negligible hemolysis of magnetic microspheres. The embolization model on rabbit auricular artery demonstrates that the magnetic microspheres can occlude the targeted blood vessel and are visualized under CT/MR imaging. All these findings suggest that the prepared magnetic microspheres could be used as the embolic agent in TACE. STATEMENT OF SIGNIFICANCE: The existing magnetic embolic microspheres suffer the poor control of hyperthermia temperature and drug release behavior in TACE. In this work, we developed the magnetic embolic microspheres based on superparamagnetic iron oxide nanoparticles with a low Curie temperature. Upon the application of alternating magnetic field, the embolic microspheres can self-regulate the hyperthermia temperature at around 50°C and the drug loaded in the microspheres can be released in a somewhat controllable manner. The embolic microspheres are also detectable to both CT and MR. These characteristics enable the developed microspheres to simultaneously realize self-regulating temperature hyperthermia, on-demand drug release, embolization, and CT/MR imaging.

Electrospinning fabrication of magnetic nanoparticles-embedded polycaprolactone (PCL) sorbent with enhanced sorption capacity and recovery speed for spilled oil removal.

The use of oil-soaked sorbents in the recovery and cleaning of oil spills presents challenges due to disposal. Recently, magnetic nanoparticle (MNP) based collection has been gaining interest as a new technique to lower the amount of labor required to treat oil spills. In this study, we devised a new method for the preparation of a magnetic nanoparticle (MNP) embedded polycaprolactone (PCL) sorbent with oleophilic and environmentally friendly features, capable of bring easily collected under a magnetic field. Compared with conventional polypropylene sorbents, the MNP embedded PCL sorbent (MNP/PCL) displayed excellent Arabian light (AL) crude oil sorption capacity (45.7 g g-1) and decreased the absorption time of the oil-soaked sorbent due to its electrospun structure and efficient distribution of hydrophobic MNPs. Furthermore, the MNP/PCL based sorbent became fully pyrolyzed under certain temperatures and conditions. The MNP embedded PCL-based sorbent demonstrated broad applicability and utility in large scale oil spill projects.

Water-based Fe3O4 magnetic fluid-coated Aspergillus niger spores for treating liquid contaminated with Cr(VI).

The use of magnetic biosorbents for the remediation of heavy metals has attracted increasing attention due to their ease of separation and reusability. We developed a method for preparing superparamagnetic biosorbent materials using water-based magnetic fluids. Water-based magnetic fluid-spores (WMFSs) were obtained by combining water-based magnetic fluid (WMF) with Aspergillus niger spores at ratios of 0.6:1 (WMFS1), 0.8:1 (WMFS2), 1:1 (WMFS3), 1.2:1 (WMFS4), and 1.4:1 (WMFS5). A magnetic composite material was prepared from magnetic nanoparticles and spores in a ratio of 1:1 as a control. The adsorption efficiency and separation effect of WMFS3 were significantly better than those of the magnetic composite material. The morphology and structure of WMFS3 were characterized by performing transmission electron microscopy. The results showed that Fe3O4 magnetic particles were uniformly coated on the spore surface. The superparamagnetism of WMFS3 was tested using a vibrating sample magnetometer. At pH 2.0, the maximum adsorption capacity of WMFS3 for Cr(VI) was 105 mg/g; in the pH range of 2.0-3.0, the adsorption equilibrium time of WMFS3 was 60 min. Thus, the adsorption process conformed to the pseudo-second-order kinetic model and Freundlich isotherm. Thermodynamic studies showed that the process was spontaneous and endothermic. The adsorption mechanisms of WMF3 for Cr(VI) included electrostatic, reduction, and complexation adsorption. This biosorbent material showed excellent adsorption performance for Cr(VI) and is promising for wastewater resource applications.

Screening of the active Ingredients in Huanglian Jiedu decoction through amide bond-Immobilized magnetic nanoparticle-assisted cell membrane chromatography.

Introduction: The Huanglian Jiedu decoction (HLJDD) is a Chinese herbal formula that exerts neuroprotective effects by alleviating oxidative stress injuries and may potentially be prescribed for treating Alzheimer's disease; however, its active ingredients have not yet been identified. Cell membrane chromatography is a high-throughput method for screening active ingredients, but traditional cell membrane chromatography requires multiple centrifugation steps, which affects its separation efficiency. Magnetic nanoparticles are unparalleled in solid-liquid separation and can overcome the shortcomings of traditional cell membrane chromatography. Methods: In this study, the neuroprotective effects of the components of HLJDD were screened through a novel magnetic nanoparticle-assisted cell membrane chromatography method. Magnetic nanoparticles and cell membranes were stably immobilized by amide bonds. Magnetic bead (MB)-immobilized cell membranes of HT-22 cells were incubated with the HLJDD extract to isolate specific binding components. The specific binding components were then identified by ultraperformance liquid chromatography (UPLC)-Orbitrap Fusion Tribrid MS after solid-phase extraction. The bioactivity of these components was analyzed in an HT-22 cellular model of glutamate-induced injury. Results and Discussion: The preparation method of the composite of cell membrane and MBs has the advantages of simple preparation and no introduction of toxic organic reagents. MBs not only provide support for cell membranes, but also greatly improve the separation efficiency compared with traditional cell membrane chromatography. Fifteen of these components were found to specifically bind to the cell membranes, and seven of them were confirmed to reduce varying degrees of glutamate-induced toxicity in HT-22 cells. In conclusion, our findings suggest that the amide bond-based immobilization of magnetic nanoparticles on cell membranes, along with solid-phase extraction and UPLC, is an effective method for isolating and discovering the bioactive components of traditional Chinese medicines.

Research progress in integrated diagnosis and treatment platform based on magnetic nanoparticles / 国际生物医学工程杂志

Theranotics, an integrated diagnosis and treatment nanoplatform technology based on nanomaterials, integrates the diagnosis and treatment of diseases seamlessly and shows a broad prospect in medical practice. With the rapid development of nanomedicine, the technology of magnetic nanoparticles (MNPs) synthesis is becoming more and more mature. MNPs have controllable shape and particle size, admirable stability and biocompatibility, excellent magnetic properties, and can be readily chemically modified. These advantages make them widely used in clinical practice, such as diagnosis, targeted drug delivery, medical imaging, hyperthermia therapy, and radiotherapy, which also make MNPs high-quality materials for integrated diagnosis and treatment platforms.In this paper, the research progress of MNPs in the areas of magnetically guided drug delivery, magnetic thermotherapy, and multimodal imaging was reviewed; their advantages as an integrated platform for diagnosis and treatment were discussed; and the problems faced in research and application prospects were summarized and outlooked.

Synthesis of novel adsorbent by incorporation of plant extracts in amino-functionalized silica-coated magnetic nanomaterial for the removal of Zn2+and Cu2+from aqueous solution.

Magnetic nanoparticles owing to their superparamagnetic behaviour and specific reactive sites are facilitated to regenerate and reuse. Our present study determines the cointegration of the plant extracts of Cynodon dactylon and Muraya koenigii with the magnetic nanoparticle coated with silica layer and surface engineered with a specific amine group. The cointegrated magnetic nano adsorbent is characterized for its analytical feature and batch studies are performed to remove zinc (Zn2+) copper (Cu2+) metal ions. Fourier transform infrared spectroscopy reveals the presence of functional entities such as NH2, Si-O-Si, C=C. The size of the cointegrated nano adsorbent (12-30 nm) was confirmed by field emission scanning electron microscopy whereas, a high-resolution transmission electron microscope affirms the nanosize of the particle constituted around 20 nm. Energy dispersive x-ray analysis confirms the presence of elements like Fe, N, Si and was confirmed by X-ray diffraction analysis and vibrating sample magnetometer affirms the superparamagnetic nature with the high magnetic saturation value (Ms - 30 emug-1). The cointegrated nano adsorbent reveals the maximum adsorption capacity of Zn2+ as 78.24 mg.g-1 and Cu2+ as 81.76 mg.g-1 of the adsorbent under the optimized conditions of contact time 45 min, pH 6.0 and temperature 35 °C. Kinetics such as pseudo-first-order, pseudo-second-order, Elovich, intraparticle diffusion and isotherm studies like Langmuir, Freundlich, Dubinin-Radushkevich and Temkin were performed to understand the mechanism of interaction between the nanoadsorbent and metal ions. The reaction system follows the pseudo-second-order kinetics and Langmuir isotherm model for both the Cu2+ and Zn2+ metal ions. To determine the reusing capacity of the cointegrated nanoadsorbent, the adsorption efficiency was studied for continuous twelve cycles with 80% recovery after subsequent acid treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40201-021-00696-9.

Magnetism and NIR dual-response polypyrrole-coated Fe3O4 nanoparticles for bacteria removal and inactivation.

Microbial contamination of water represents a great threat to the public health that has attracted worldwide attention. In this work, polypyrrole magnetic nanoparticles (Fe3O4@PPy NPs) with sterilization properties were fabricated. More specifically, the Fe3O4@PPy NPs obtained via aqueous dispersion polymerization and an in situ chemical oxidative polymerization exhibited a cationic surface and high photothermal conversion efficiency. More than 50% of bacteria adsorption can be achieved at a dosage of 100 µg/mL Fe3O4@PPy NPs under magnetic field, and high photothermal sterilization efficacy (~100%) can be obtained upon NIR exposure at the same dosage for 10 min. Noteworthy, the Fe3O4@PPy NPs can be recycled by magnetism and reused without affecting their photothermal sterilization capability. This study clearly provides experimental evidence of the great potential of Fe3O4@PPy NPs as stable and reusable nanocomposite materials for bacteria adsorption and photothermal sterilization performance. The application of Fe3O4@PPy NPs can realize enviromental-friendly bacterial contaminated water treatment as well as provide stratgies for synergistical antibacterial materials design.

Recent applications of magnetic solid phase extraction in sample preparation for phytochemical analysis.

Sample preparation such as isolation and pre-concentration is a crucial step for the phytochemical analysis. Magnetic solid-phase extraction (MSPE) has received considerable attention, mainly due to its phase separation more conveniently by facile magnetic decantation as compared to traditional SPE. This review focused on the recent applications of MSPE in sample preparation for the analysis of phytochemical compounds in plants, biological samples and Chinese herbal preparations. In addition, the enzymes immobilized on the magnetic materials and used for the biospecific extraction of enzyme inhibitors were also discussed. The information summarized in this article may provide a reference to the further applications of MSPE in phytochemical analysis.

Advances in Magnetic Nanoparticle-Mediated Cancer Immune-Theranostics.

Cancer immunotherapy is a cutting-edge strategy that eliminates cancer cells by amplifying the host's immune system. However, the low response rate and risks of inducing systemic toxicity have raised uncertainty in the treatment. Magnetic nanoparticles (MNPs) as a versatile theranostic tool can be used to target delivery of multiple immunotherapeutics and monitor cell/tissue responses. These capabilities enable the real-time characterization of the factors that contribute to immunoactivity so that future treatments can be optimized. The magnetic properties of MNPs further allow the implementation of magnetic navigation and magnetic hyperthermia for boosting the efficacy of immunotherapy. The multimodal approach opens an avenue to induce robust immune responses, minimize safety issues, and monitor immune activities simultaneously. Thus, the object of this review is to provide an overview of the burgeoning fields and to highlight novel technologies for next-generation immunotherapy. The review further correlates the properties of MNPs with the latest treatment strategies to explore the crosstalk between magnetic nanomaterials and the immune system. This comprehensive review of MNP-derived immunotherapy covers the obstacles and opportunities for future development and clinical translation.

Numerical simulation of the effect of necrosis area in systemic delivery of magnetic nanoparticles in hyperthermia cancer treatment.

In a magnetic hyperthermia treatment, malignant cancerous cells are ablated by the heat production of magnetic nanoparticles (MNP) under an external magnetic field. This novel approach is a promising tool to eliminate the tumor cells by a higher temperature inside the tumor microenvironment. MNPs are needed inside the tumor microenvironment to increase the heat, and this could be possible with intravenous drug injection. However, tumors with necrosis regions are more resistant to drug penetration, and this can cause inadequate and non-homogeneous temperature distribution in the tumor. Hence, in this study, we used numerical methods to investigate the Spatio-temporal temperature field distribution in the necrotic tumor and its surrounding tissue. To this end, an intravenous bolus injection is used to simulate the effect of systemic drug delivery in tumors with necrosis region. Results show that the temperature field with the necrosis region with 10% of the tumor radius is more prone to higher temperature values. The hypoxia region is affected by the high temperature despite the necrosis region in the tumor. However, a broader necrosis region impedes drug penetration inside the inner layers of tumors, which leads to a lower heat generation by the MNPs. Results also demonstrate that only 15.5% of MNP concentration distributed to the necrosis with 50% of tumor radius, leading a temperature of 42∘C in the necrosis region, which is not sufficient for the tumor ablation. Therefore, the temperature distribution is dependant on the sizes of necrosis regions in tumors, and tumors with a larger necrotic region (over 20% of tumor radius) are challenging to treat with hyperthermia treatment. This study could help the future in vitro and in vivo studies of hyperthermia treatment in necrotic tumors.

Method for Ferrite Nanomaterials-Mediated Cellular Magnetic Hyperthermia.

Magnetic hyperthermia (MH) mediated by magnetic nanoparticles is one of the most promising antitumor modalities. The past several decades have witnessed great progress for MH antitumor therapy in scientific trials and clinic applications since it was initially advanced by Gilchrist et al. The ultimate object of MH in vivo is to efficiently kill cancer cells, and hence, it is of great importance to develop an optimized cellular MH method to evaluate the therapeutic efficiency in vitro. In this study, we systematically studied the considerable affecting factors of cancer cell-killing efficiency during the cellular MH process, including the region of cell vessel positioned inside the alternating magnetic field copper coil, the magnetic field amplitude, the types of cancer cells, etc. Taking all these into account, we introduced a method for standardizing the cellular MH process to evaluate the cell-killing efficiency.

Residence Time-Extended Nanoparticles by Magnetic Field Improve the Eradication Efficiency of Helicobacter pylori.

Helicobacter pylori infection is one of the leading causes of several gastroduodenal diseases, such as gastritis, peptic ulcer, and gastric cancer. In fact, H. pylori eradication provides a preventive effect against the incidence of gastric cancer. Amoxicillin is a commonly used antibiotic for H. pylori eradication. However, due to its easy degradation by gastric acid, it is necessary to administer it in a large dosage and to combine it with other antibiotics. This complexity and the strong side effects of H. pylori eradication therapy often lead to treatment failure. In this study, the chitosan/poly (acrylic acid) particles co-loaded with superparamagnetic iron oxide nanoparticles and amoxicillin (SPIO/AMO@PAA/CHI) are used as drug nano-carriers for H. pylori eradication therapy. In vitro and in vivo results show that the designed SPIO/AMO@PAA/CHI nanoparticles are biocompatible and could retain the biofilm inhibition and the bactericidal effect of amoxicillin against H. pylori. Moreover, the mucoadhesive property of chitosan allows SPIO/AMO@PAA/CHI nanoparticles to adhere to the gastric mucus layer and rapidly pass through the mucus layer after exposure to a magnetic field. When PAA is added, it competes with amoxicillin for chitosan, so that amoxicillin is quickly and continuously released between the mucus layer and the gastric epithelium and directly acts on H. pylori. Consequently, the use of this nano-carrier can extend the drug residence time in the stomach, reducing the drug dose and treatment period of H. pylori eradication therapy.

Synthesis and characterization of thermo/pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) coated magnetic nanoparticles.

Herein, thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer-coated magnetic nanoparticles were synthesized via a green and rapid synthetic approach based on microwave irradiation. Firstly, a novel thermo- and pH-sensitive pectin-graft-poly(dimethylaminoethyl methacrylate) copolymer (Pec-g-PolyDMAEMA) was synthesized and then, Pec-g-PolyDMAEMA based magnetic nanoparticles (Pec-g-PolyDMAEMA@Fe3O4) were produced via microwave-assisted co-precipitation method. The thermo/pH/magnetic field multi-sensitive hybrid nanoparticle was characterized by techniques like TEM, VSM, FT-IR, and TGA/DSC. In vitro release studies of 5-Fluorouracil (FL) were carried out by altering the temperature (37 and 44°C), pH (5.5 and 7.4) and presence of an AMF. The FL release of Pec-g-PolyDMAEMA@Fe3O4@FL exhibited pH-sensitive behavior. They showed thermo/pH-sensitive FL release features with the greatest release of FL at 37°C (56%) than at 44°C (40%) and at pH of 7.4 (63%) than at pH of 5.5 (45%) within 48h. The FL release was also significantly increased (100%) with the presence of a 50 mT magnetic field. These results indicate that the developed Pec-g-PolyDMAEMA@Fe3O4 nanoparticles are promising in the application of multi-stimuli-sensitive delivery of drugs.

mNP hyperthermia and hypofractionated radiation activate similar immunogenetic and cytotoxic pathways.

OBJECTIVE: The goal of this study is to better understand the immunogenetic expression and related cytotoxic responses of moderate but clinically relevant doses of hypofractionated radiation (1x15 Gy and 3x8 Gy) and magnetic nanoparticle hyperthermia (mNPH, CEM43 30). METHODS: Genetic, protein, immunopathology and tumor growth delay assessments were used to determine the immune and cytotoxic responses following radiation and mNPH alone and in combination. Although the thermal dose used, 43 C°/30 min (CEM43 30), typically results in modest independent cytotoxicity, it has shown the ability to stimulate an immune response and enhance other cancer treatments. The radiation doses studied (15 Gy and 3x8 Gy) are commonly used in preclinical research and are effective in selected stereotactic and palliative treatment settings, however they are not commonly used as first-line primary tumor treatment regimens. RESULTS: Our RNA-based genetic results suggest that while many of the cytotoxic and immune gene and protein pathways for radiation and hyperthermia are similar, radiation, at the doses used, results in a more consistent and expansive anti-cancer immune/cytotoxic expression profile. These results were supported by immunohistochemistry based cytotoxic T-cell tumor infiltration and tumor growth delay studies. When used together radiation and hyperthermia led to greater immune and cytotoxic activity than either modality alone. CONCLUSION: This study clearly shows that modest, but commonly used hypofractionated radiation and hyperthermia doses share many important immune and cytotoxic pathways and that combining the treatments, as compared to either treatment alone, results in genetic and biological anti-cancer benefits.