Hierarchical self-assembled hollow hydroxyapatite flower microspheres containing terpene functional groups for efficient drug loading and pH-responsive drug release

In this paper, we fabricated hierarchical self-assembled hollow rose-like flower microspheres (HRFM) and hollow burr-like flower microspheres (HBFM) hydroxyapatite (HAP) using dehydroabietyl phosphate tri-ester (DDPT) as an organic phosphorus source, a regulating agent, and a soft template simultaneously via a one-step solvothermal method. The HBFM and HRFM have been explored for their application in drug delivery, using doxorubicin (DOX) as a drug model. The formation mechanisms of HRFM and HBFM were proposed on the basis of the electrostatic potential diagrams and self-assembled behavior of DDPT organic molecule. After the rosin-based terpene functional groups were incorporated, both HRFM and HBFM exhibited low cytotoxicity against Hela cell, pH-dependent sustained drug release properties, and high drug loading capacity. The drug-loading capacities of HBFM and HRFM were 116.6?mg?g^?1 and 148.3?mg?g^?1, respectively. Thus, the as-prepared HRFM and HBFM are promising for the applications in drug delivery.     

Novel approach in synthesizing ternary GO-Fe3O4-PPy nanocomposites for high Photothermal performance

In this study, graphene oxide-iron oxide-polypyrrole (GO-Fe₃O₄-PPy) ternary nanocomposites having high photothermal activity and stability are synthesized and analyzed using ultraviolet–visible (UV–Vis) spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction spectroscopy (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and magnetic hysteresis measurement (VSM). The effect of power density (1.5–2.5 W cm⁻²), concentration (0.01–0.2 mg mL⁻¹), and component composition of nanocomposites on the photothermal properties in the near-infrared (NIR) region (808 nm) is examined. The results show that superparamagnetic GO-Fe₃O₄-PPy ternary nanocomposite exhibits excellent photothermal performance. The temperature reaches to 55.5, 72.3, and 83.1 °C under the irradiation of the 808 nm NIR laser at 1.5, 2.0^—, and 2.5 W cm⁻² of power density for 10 min at 0.1 mg mL⁻¹ photothermal therapy (PTT) agent, respectively, and moreover it has excellent photothermal stability. In summary, it is concluded that synthesized nanocomposites potentially may be used in simultaneous magnetic field-guided treatments. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 137, 48837.     

Kidney-Protector Lipidic Cilastatin Derivatives as Structure-Directing Agents for the Synthesis of Mesoporous Silica Nanoparticles for Drug Delivery

Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacological activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnology strategies focused on combating the different illnesses this methodology emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.     

Insight on the Dependence of the Drug Delivery Applications of Mesoporous Silica Nanoparticles on Their Physical Properties

Silicon - Mesoporous silica nanoparticles (MSNs) are fascinating due to their interesting properties and applications. The optimization of MSNs for drug delivery applications was achieved by...     

Facile synthesis of novel fluorescent phenol formaldehyde resin nanospheres for drug release

A highly-efficient nano-medical carrier system was constructed for drug release based on a facile synthesis, excellent fluorescence, and structure of phenol formaldehyde resin (PFR). The PFR was easily synthesized through a simple one-step hydrothermal reaction, reduction and etching process, and a silane coupling agent modification process. The multiple functionalized drug delivery system, defined as PFR-NH₂@DOX was constructed by loading Adriamycin (DOX) into PFR. Drug release results in vitro displayed a DOX content of 145 mg g⁻¹ prodrug nanosphere has excellent pH-triggered drug release (about 84.71%) within 72 h at pH 5 solution. The fluorescence recovery of PFR after DOX release indicates the potential application in fluorescence imaging and controlled drug release.     

Melanin-Like Nanomedicine in Photothermal Therapy Applications

Photothermal therapy (PTT) mediated by nanomaterial has become an attractive tumor treatment method due to its obvious advantages. Among various nanomaterials, melanin-like nanoparticles with nature biocompatibility and photothermal conversion properties have attracted more and more attention. Melanin is a natural biological macromolecule widely distributed in the body and displays many fascinating physicochemical properties such as excellent biocompatibility and prominent photothermal conversion ability. Due to the similar properties, Melanin-like nanoparticles have been extensively studied and become promising candidates for clinical application. In this review, we give a comprehensive introduction to the recent advancements of melanin-like nanoparticles in the field of photothermal therapy in the past decade. In this review, the synthesis pathway, internal mechanism and basic physical and chemical properties of melanin-like nanomaterials are systematically classified and evaluated. It also summarizes the application of melanin-like nanoparticles in bioimaging and tumor photothermal therapy (PTT)in detail and discussed the challenges they faced in clinical translation rationally. Overall, melanin-like nanoparticles still have significant room for development in the field of biomedicine and are expected to applied in clinical PTT in the future.     

Multifunctional mesoporous silica nanocomposite nanoparticles for theranostic applications

Clever combinations of different types of functional nanostructured materials will enable the development of multifunctional nanomedical platforms for multimodal imaging or simultaneous diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) possess unique structural features such as their large surface areas, tunable nanometer-scale pore sizes, and well-defined surface properties. Therefore, they are ideal platforms for constructing multifunctional materials that incorporate a variety of functional nanostructured materials. In this Account, we discuss recent progress by our group and other researchers in the design and fabrication of multifunctional nanocomposite nanoparticles based on mesoporous silica nanostructures for applications to simultaneous diagnosis and therapy. Versatile mesoporous silica-based nanocomposite nanoparticles were fabricated using various methods. Here, we highlight two synthetic approaches: the encapsulation of functional nanoparticles within a mesoporous silica shell and the assembly of nanoparticles on the surface of silica nanostructures. Various nanoparticles were encapsulated in MSNs using surfactants as both phase transfer agents and pore-generating templates. Using MSNs as a scaffold, functional components such as magnetic nanoparticles and fluorescent dyes have been integrated within these systems to generate multifunctional nanocomposite systems that maintain their individual functional characteristics. For example, uniform mesoporous dye-doped silica nanoparticles immobilized with multiple magnetite nanocrystals on their surfaces have been fabricated for their use as a vehicle capable of simultaneous magnetic resonance (MR) and fluorescence imaging and drug delivery. The resulting nanoparticle-incorporated MSNs were then tested in mice with tumors. These in vivo experiments revealed that these multifunctional nanocomposite nanoparticles were delivered to the tumor sites via passive targeting. These nanocomposite nanoparticles served as successful multimodal imaging probes and also delivered anticancer drugs to the tumor site. With innumerable combinations of imaging modalities and drug delivery available within these vehicles, multifunctional nanocomposite nanoparticles provide new opportunities for clinical diagnostics and therapeutics.     

Preparation of mesoporous silica nanoparticles with controlled pore size,particle diameter,morphology, and structure by two-step process of chlorosilane residue

In this study, mesoporous silica nanoparticles (MSNs) were successfully prepared in two steps using chlorosilane residue. First, chlorosilane residue was subjected to alcoholysis with n-propanol to synthesize tetrapropoxysilane (TPOS), followed by the synthesis of MSNs using TPOS as silicon source. Alcoholysis experiment was designed and optimized using orthogonal experimental method. In addition, effects of four factors (i.e., molar ratio of n-propanol to chlorosilane residue; feed rate of n-propanol; reaction temperature; and molar ratio of n-hexane to chlorosilane residue) on the yield of TPOS were investigated. The optimum alcoholysis conditions were determined. Yield of TPOS was 56% under the optimum alcoholysis conditions. Results obtained from single factor analysis of variance revealed that molar ratio of n-propanol to chlorosilane residue was the most significant factor affecting TPOS yield. Next, a series of spherical MSNs with dendritic structure and irregular mesoporous/microporous silica nanoparticles with non-dendritic structure were successfully synthesized via precise regulation of various experimental parameters in emulsion systems. In this regard, the adjustment of n-hexanol/1,3,5-triisopropylbenzene (TIPB) molar ratio or n-octane/n-hexanol/TIPB molar ratio was found to be effective for achieving controllable regulation of morphology (spherical or irregular); structure (dendritic or non-dendritic); pore size (mesoporous (4.6–9.2?nm) or microporous (1.6–1.7?nm)); and particle diameter (60–134?nm) of silica nanoparticles. However, the adjustment of n-octane/TIPB molar ratio marginally affected spherical morphology, dendritic structure, and pore size (4.0–4.6?nm) of synthesized MSNs, with considerable effect on particle diameter (61–151?nm). In addition, as-synthesized MSNs exhibited large specific surface area (708–857?m²/g) and large pore volume (1.5–3.6 cm³/g).     

Mesoporous Silica Nanoparticles: Drug Delivery Vehicles for Antidiabetic Molecules

Mesoporous silica nanoparticles (MSNs) are promising nanomaterials that are widely used in biomedical applications like drug delivery, diagnosis, bio-sensing and cell tracking. MSNs have been investigated meticulously in the drug-delivery field due to their unique chemical and pharmacokinetic properties, such as highly ordered mesopores, high surface area and pore volume, tuneable pore size, stability, surface functionalisation, and biocompatibility. MSN-based nanocomposites have been used to deliver therapeutic molecules like insulin, GLP-1, exenatide, DPP-4 inhibitor and plasmid-containing GLP-1 genes for managing diabetes mellitus for the last decade. The functionalisation properties of MSNs make them substantially capable of the co-delivery, controlled delivery and stimuli-responsive delivery of antidiabetic drugs. This review focuses on the delivery of antidiabetic therapeutics with special emphasis on the functionalisation of MSNs and stimuli-responsive delivery.     

Mesoporous silica nanoparticles for bioadsorption, enzyme immobilisation, and delivery carriers

Mesoporous silica nanoparticles (MSNs) provide a non-invasive and biocompatible delivery platform for a broad range of applications in therapeutics, pharmaceuticals and diagnosis. The creation of smart, stimuli-responsive systems that respond to subtle changes in the local cellular environment are likely to yield long term solutions to many of the current drug/gene/DNA/RNA delivery problems. In addition, MSNs have proven to be promising supports for enzyme immobilisation, enabling the enzymes to retain their activity, affording them greater potential for wide applications in biocatalysis and energy. This review provides a comprehensive summary of the advances made in the last decade and a future outlook on possible applications of MSNs as nanocontainers for storage and delivery of biomolecules. We discuss some of the important factors affecting the adsorption and release of biomolecules in MSNs and review of the cytotoxicity aspects of such nanomaterials. The review also highlights some promising work on enzyme immobilisation using mesoporous silica nanoparticles.     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.     

Hyperbranched poly (amine-ester)-poly(ε-caprolactone) copolymer and their nanoparticles as camptothecin delivery system

A new amphiphilic hyperbranched poly (amine-ester)-poly(ε-caprolactone) copolymer (HPAE-co-PCL) was synthesized by ring-opening polymerization of ε-caprolactone and branched poly (amine-ester) (HPAE-OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT-IR, ¹H-NMR (¹³C-NMR), thermo gravimetric analysis apparatus (TGA) and differential scanning calorimetry (DSC). Camptothecin (CPT)-loaded copolymer nanoparticles were prepared by the oil-in water (o/w) emulsion technique method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). CPT-loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug-loading content, and drug release behavior. As the molar ratio of ε-caprolactone to HPAE increased, the nanoparticles size and drug-loading content increased, and the drug release rate decreased. The antitumor activity of the CPT-loaded HPAE-co-PCL nanoparticles against human hepatoma HEPG2 cells was evaluated by 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The CPT-loaded HPAE-co-PCL nanoparticles showed comparable anticancer efficacy with the free drug.     

Facile synthesis of pseudocapacitive Mn3O4 nanoparticles for high-performance supercapacitor

In this work, a facile method to produce the ultrafine (4–14 nm) and mixed valence Mn₃O₄ nanoparticles from low-cost MnSiO₃ (manganese silicate) particles were introduced. The best NaOH concentration in hydrothermal treatment has been determined after a series of experiments. Also, the as-synthesized Mn₃O₄ material with good specific capacitance has been investigated attentively at a high mass loading (∼3 mg cm⁻²). The particles size and the pore size distribution is found to be refined and optimized, respectively. This increased the crystallinity and the capacitive contribution in the energy process. Thereby improving the rate capability and cycling stability, which result in significant improvement of specific capacitance (401 F g⁻¹ at 10 mV s⁻¹). The aqueous asymmetric supercapacitor device AC//Mn₃O₄ with a stable working voltage window up to 2.0 V has been fabricated, and it is found to have an energy density of 40.2 W h kg⁻¹ at 500 W kg⁻¹ power density. This could sustain 5000 cycles galvanostatic charge/discharge with 96.9% retention.     

An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells. The AuNP-mTHPC complex is biocompatible, soluble, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650-nm laser, which decreased mitochondrial membrane potential (^∆ψ_m). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Our study aimed at applying the AuNP-mTHPC approach as a potential treatment of cancer in the biomedical field.     

An efficient and universal solar interfacial photothermal reactor toward liquid phase oxidation

Photothermal catalysis has attracted great attention owing to high solar energy utilization efficiency, and great progress has been achieved in gas-phase catalysis. However, photothermal catalysis in liquid-phase shows a limited performance, due to high specific heat capacity of liquid. Herein, an interfacial photothermal catalytic (IPC) strategy applying an IPC leaf was designed for liquid-phase catalysis using benzyl alcohol oxidation as the model reaction. On even ground, the benzaldehyde generation rate (8.7 mmol g_cat⁻¹ h⁻¹) of the IPC system with Ce-doped MnO₂ as photothermal catalyst was almost 4.8 times and 3 times of bulk photothermal catalysis and the relative bulk thermal catalysis. Experimental results proved that this excellent catalytic performance could be attributed to both the high temperature achieved and the enhanced lattice oxygen activity by solar irradiation. This IPC system also exhibited good universality and long-term durability. Our work innovatively created a green strategy to obtain fine chemicals with only solar irradiation.     

Hyperbranched poly(glycerol esteramide): A biocompatible drug carrier from glycerol feedstock and dicarboxylic acid

Polymer carrier with biodegradable, biocompatible as well as solubility enhancing properties are highly looked upon in the pharmaceutical industry to improve the drug delivery systems. A series of hyperbranched poly(glycerol esteramide) (HPGEA) with M_w of 5000–12,000 Da, degree of branching of 57%–62%, and hydroxyl values of 200–280 mg KOH/g sample were synthesized through polycondensation of N,N-bis(2-hydroxyethyl)stearamide (diethanolamide) and poly(glycerol ester) (PGE). The HPGEAs were characterized by ATR-FTIR, GPC, ¹H and ¹³C-NMR, and DSC. The enthalpy of fusion of HPGEAs (43–84 J g⁻¹) were lower than the commercial polymers (193–391 J g⁻¹), indicating its potential as drug carrier for solid dispersion (SD). HPGEA-based SDs showed substantial enhancement in solubility and release rate than pure drug, commercial polymer-based SDs, as well as commercial formulation. The safety of HPGEAs and HPGEA-based SDs were proven through MTT assay with IC₅₀ of 2400–9800 and 1200–3500 μg ml⁻¹, respectively.     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Effect of porogenic solvent on the morphology,recognition and release properties of carbamazepine‐molecularly imprinted polymer nanospheres

This study focus on the effect of the porogenic solvent on the morphology, recognition, and drug release of carbamazepine‐molecularly imprinted polymer nanospheres prepared by precipitation polymerization. The scanning electron microscopy (SEM) images and Brunauer‐Emmett‐Teller (BET) analysis showed that molecularly imprinted polymer (MIP) prepared by acetonitrile exhibited a regular spherical shape at the nanoscale with a high degree of monodispersity, specific surface area of 242 m² g⁻¹, and pore volume of 1 mL g⁻¹, while those using chloroform and toluene produced irregular polymer particles with low specific surface area and pore volume. MIP prepared by acetonitrile/chloroform (1 : 1, v/v) showed mediator texture properties compared to MIPs obtained by acetonitrile or chloroform. Results from saturation and displacement assays indicated that the imprinted nanospheres with binding capacity of 2.85 (mg CBZ/g polymer) had high specific affinity to CBZ in contrast to nonimprinted nanospheres (1.63 mg CBZ/g polymer). The imprinted nanospheres with 2.4 selectivity factor had good recognition to CBZ than analog template of oxcarbazepine. Moreover, release studies showed that 20% of loaded CBZ was released from the imprinted nanospheres within the initial 6 h, while another 80% of CBZ was released in the following 9 days. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Electrochemical performance of Bi2Te3/GO composite anode for LIB application

Present investigation deals with the study of electrochemical properties of Bi₂Te₃/GO composite for its use as anode material in Li-ion batteries. The Bi₂Te₃/GO composite has been synthesized via polyol route. The surface morphology and structural properties of the as-prepared samples have been studied by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy techniques. The phase of as-synthesized composite was found out to be rhombohedral as has been characterized by X-ray diffractometer. The presence of GO in the Bi₂Te₃ matrix has been confirmed by the presence of characteristic D and G bands in the Raman spectra. The as-synthesized composite showed the first cycle discharge/charge capacity of 752/514 mAh g⁻¹ at the current density of 0.1 Ag⁻¹, superior rate capability (~50 mAh g⁻¹ at 2 Ag⁻¹), and excellent cycling stability over 500 cycles at 0.1 Ag⁻¹. The presence of GO in the matrix helps to enhance the electronic conductivity due to the rapid Li-ion diffusion and helps to shield the changes in volume during the cycling processes.     

Simultaneous co-substitution of Sr2+/Fe3+ in hydroxyapatite nanoparticles for potential biomedical applications

In human, strontium (Sr) follows the same physiological pathway as calcium and thus could be used for improving the bioactivity and osteoconductivity of hydroxyapatite (HAp) in bone tissues. Similarly, iron (Fe) can potentially play an important role in bone remodeling due to its magnetic properties. Therefore, the current study was aimed to simultaneously co-substitute Sr²⁺/Fe³⁺ in HAp nanoparticles for various potential biomedical applications. The Sr²⁺/Fe³⁺ co-substituted HAp nanoparticles were systematically synthesized through sonication-assisted aqueous precipitation method. The as-synthesized nanoparticles were evaluated for different physicochemical and biological properties. X-ray diffraction (XRD) patterns of Sr²⁺/Fe³⁺ co-substituted HAp nanoparticles confirmed their phase purity and showed hexagonal-like structure. Scanning electron microscope (SEM) micrographs showed an agglomerated rod-like morphology of HAp nanoparticles which contained pores consisted of small spheroids. The nanoparticles displayed magnetization (Ms) reliance on the loading level of mole % (X?=?Fe³⁺) and exhibited tunable porosity and microhardness (Hv) upon heat treatment. The nanoparticles showed less than 5% hemolysis demonstrating high blood compatibility with high in vitro bioactivity performance. The multifunctional properties of synthesized nanoparticles make them a potential candidate for various biomedical applications; including bone grafting and guided bone regeneration, targeted drug delivery, magnetic resonance imaging, and hyperthermia based cancer treatment.