A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.     

Synthesis and characterization of biocompatible hydroxyapatite coated ferrite

Ferrite particles coated with biocompatible phases can be used for hyperthermia treatment of cancer. We have synthesized substituted calcium hexaferrite, which is not stable on its own but is stabilized with small substitution of La. Hexaferrite of chemical composition (CaO)_0.75(La₂0₃)_0.20(Fe₂O₃)₆ was prepared using citrate gel method. Hydroxyapatite was prepared by precipitating it from aqueous solution of Ca(NO₃)₂ and (NH₄)₂HPO₄ maintaining pH above 11. Four different methods were used for coating of hydroxyapatite on ferrite particles. SEM with EDX and X-ray diffraction analysis shows clear evidence of coating of hydroxyapatite on ferrite particles. These coated ferrite particles exhibited coercive field up to 2 kOe, which could be made useful for hysteresis heating in hyperthermia. Studies by culturing BHK-21 cells and WBC over the samples show evidence of biocompatibility. SEM micrographs and cell counts give clear indication of cell growth on the surface of the sample. Finally coated ferrite particle was implanted in Kasaulli mouse to test its biocompatibility. The magnetic properties and biocompatibility studies show that these hydroxyapatite coated ferrites could be useful for hyperthermia.     

Nanoheterojunction Engineering Enables NIR-II-Triggered Photonic Hyperthermia and Pyroelectric Catalysis for Tumor-Synergistic Therapy

Photodynamic therapy (PDT) as a non-invasive strategy shows high promise in cancer treatment. However, owing to the hypoxic tumor microenvironment and light irradiation-mediated rapid electron–hole pair recombination, the therapeutic efficacy of PDT is dramatically discounted by limited reactive oxygen species (ROS) generation. Herein, a multifunctional theranostic nanoheterojunction is rationally developed, in which 2D niobium carbide (Nb₂C) MXene is in situ grown with barium titanate (BTO) to generate a robust photo-pyroelectric catalyst, termed as BTO@Nb₂C nanosheets, for enhanced ROS production, originating from the effective electron–hole pair separation induced by the pyroelectric effect. Under the second near-infrared (NIR-II) laser irradiation, Nb₂C MXene core-mediated photonic hyperthermia regulates temperature variation around BTO shells facilitating the electron–hole spatial separation, which reacts with the surrounding O₂ and H₂O molecules to yield toxic ROS, achieving a synergetic effect by means of combinaterial photothermal therapy with pyrocatalytic therapy. Correspondingly, the engineered BTO@Nb₂C composite nanosheets feature benign biocompatibility and high antitumor efficiency with the tumor-inhibition rate of 94.9% in vivo, which can be applied as an imaging-guided real-time non-invasive synergetic dual-mode therapeutic nanomedicine for efficient tumor nanotherapy.     

Let There be Light: Polymeric Micelles with Upper Critical Solution Temperature as Light‐Triggered Heat Nanogenerators for Combating Drug‐Resistant Cancer

Complete drug release and efficient drug retention are two critical factors in reversing drug resistance in cancer therapy. In this regard, polymeric micelles with an upper critical solution temperature (UCST) are designed as a new exploration to reverse drug resistance. The amphiphilic UCST‐type block copolymers are used to encapsulate photothermal agent IR780 and doxorubicin (DOX) simultaneously. The integrated UCST‐type drug nanocarriers show light‐triggered multiple synergistic effects to reverse drug resistance and are expected to kill three birds with one stone: First, owing to the photothermal effect of IR780, the nanocarriers will be dissociated upon exposure to laser irradiation, leading to complete drug release. Second, the photothermal effect‐induced hyperthermia is expected to avoid the efflux of DOX and realize efficient drug retention. Last but not least, photothermal ablation of cancer cells can be achieved after laser irradiation. Therefore, the UCST‐type drug nanocarriers provide a new strategy in reversing drug resistance in cancer therapy.     

基于ARM内核的嵌入式肿瘤热疗系统

采用基于ARM内核的嵌入式系统开发小型超声热疗仪是肿瘤热疗系统开发领域中应用嵌入式技术的一个全新尝试，实现了上、下位机一体化设计。嵌入式肿瘤热疗系统包括组织温度采集与转换系统、超声功率控制信号发生模块、存储管理系统、人机交互系统（包括液晶显示及键盘输入）以及其他基本功能模块。根据热疗实际需要对PID控制算法进行改进与优化，提高了治疗中肿瘤组织温度的控制品质。实验结果表明，系统设计可靠，满足临床肿瘤热疗要求。     

pH‐ and NIR Light‐Responsive Micelles with Hyperthermia‐Triggered Tumor Penetration and Cytoplasm Drug Release to Reverse Doxorubicin Resistance in Breast Cancer

The acquisition of multidrug resistance (MDR) is a major hurdle for the successful chemotherapy of tumors. Herein, a novel hybrid micelle with pH and near‐infrared (NIR) light dual‐responsive property is reported for reversing doxorubicin (DOX) resistance in breast cancer. The hybrid micelles are designed to integrate the pH‐ and NIR light‐responsive property of an amphiphilic diblock polymer and the high DOX loading capacity of a polymeric prodrug into one single nanocomposite. At physiological condition (i.e., pH 7.4), the micelles form compact nanostructure with particle size around 30 nm to facilitate blood circulation and passive tumor targeting. Meanwhile, the micelles are quickly dissociated in weakly acidic environment (i.e., pH ≤ 6.2) to release DOX prodrug. When exposed to NIR laser irradiation, the hybrid micelles can trigger notable tumor penetration and cytosol release of DOX payload by inducing tunable hyperthermia effect. In combination with localized NIR laser irradiation, the hybrid micelles significantly inhibit the growth of DOX‐resistant MCF‐7/ADR breast cancer in an orthotopic tumor bearing mouse model. Taken together, this pH and NIR light‐responsive micelles with hyperthermia‐triggered tumor penetration and cytoplasm drug release can be an effective nanoplatform to combat cancer MDR.     

Rotary scanning wireless temperature measurement method for hyperthermia using ferromagnetic implants

Recently, the use of a ferromagnetic material in a soft‐heating method has garnered much attention as a novel method for cancer treatment. By concurrently using this material as a thermal probe, we are currently developing a minimally invasive heating and wireless temperature measurement system. To make the approach feasible in a clinical setting, it is vital to overcome the key challenge of heating the local tumor at a constant temperature. In previous conventional approaches, it was necessary to switch the induction‐heating power supply on/off after the target tumor temperature was reached. However, it cannot determine the temperature of the material during the power‐off period. Therefore, we changed this approach and found that by adjusting the distance between the heating coil and the material while maintaining a constant current flow in heating coil, the drift problem, which happened just after power is supplied during the on/off operation, did not occur any longer. Accordingly, it was not required to use multiple sensors to reduce the drift, thereby minimizing the cost. This study verifies the validity of our wireless thermometry approach while performing rotary scanning and proposes a technique for determining achievement of the target temperature. This knowledge complements other approaches for cancer treatment utilizing hyperthermia. © 2015 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Fast access to core/shell/shell CdTe/CdSe/ZnO quantum dots via magnetic hyperthermia method

The intrinsic low quantum yield (QY) of type II core shell quantum dots (QDs) composes the limitation for these heterostructured nanomaterials to be used in practical application. Herein, magnetic hyperthermia method is employed to intensify reaction process and facilely synthesize CdTe/CdSe heterostructured QDs with improved optical performance for the first time. The QY of the type II QDs is increased to 49% by further growing an inert ZnO layer. The type I interface between CdSe and ZnO helps confine electrons to the inner structure of the QDs, thus improving the QY. The successful preparation and performance enhancement of the CdTe/CdSe type II QDs via magnetic hyperthermia method demonstrate the great potential of this method for the preparation of other materials. Besides, the red‐emission QDs are used as conversion materials in white light emitting diodes to reveal their promising application in practical illumination. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2614–2621, 2016     

Reactive Extrusion Strategies to Fabricate Magnetite–Polyethylene Nanocomposites with Enhanced Mechanical and Magnetic Hyperthermia Properties

Biofouling is a major problem in water filtration units, which leads to premature system failure. Conventional treatment methods involving the use of chemicals or high‐pressure hydraulics exert mechanical strain on filter materials, leading to shortened service lifetimes. In this study, a novel magnetic polymer nanocomposite is fabricated using a blend of high density/ultrahigh molecular weight polyethylene with magnetite nanoparticle (MNP) fillers. The resulting magnetite–polyethylene nanocomposite (MPE‐NC) is mechanically robust and can be externally actuated with an alternating magnetic field to generate localized heating that is effective in eradicating bacterial biofilms. The MNPs are functionalized with silane‐based coupling agents and crosslinked onto the polyethylene backbone via a reactive extrusion approach, which results in a twofold enhancement in mechanical properties of the polymer matrix. Furthermore, the magnetic hyperthermia performance of the MPE‐NC is improved eightfold by replacing undoped magnetite nanospheres with zinc‐doped magnetite nanocube fillers, and the magnetic hyperthermia treatment approach is shown to be 12 times more effective in destroying bacterial biofilms compared to a direct heat‐treatment method. During hyperthermia treatment, the mechanical integrity of the MPE‐NC is preserved, thereby validating the potential of the MPE‐NC as a new filter material with high efficiency in biofilm removal and extended durability.