Precise control of cargo release is essential but still a great challenge for any drug delivery system. Irreversible electroporation (IRE), utilizing short high-voltage pulsed electric fields to ...destabilize the biological membrane, has been recently approved as a non-thermal technique for tumor ablation without destroying the integrity of adjacent collagenous structures. Due to the electro-permeating membrane ability, IRE might also have great potential to realize the controlled drug release in response to various input IRE parameters, which were tested in a red blood cell (RBC) model in this work. According to the mathematical simulation model of a round biconcave disc-like cell based on RBC shape and dielectric characteristics, the permeability and the pore density of the RBC membrane were found to quantitatively depend on the pulse parameters. To further provide solid experimental evidence, indocyanine green (ICG) and doxorubicin (DOX) were both loaded inside RBCs (RBC@DOX&ICG) and the drug release rates were found to be tailorable by microsecond pulsed electric field (μsPEF). In addition, μsPEF could effectively modulate the tumor stroma to augment therapy efficacy by increasing micro-vessel density and permeability, softening extracellular matrix, and alleviating tumor hypoxia. Benefiting from these advantages, this IRE-responsive RBC@DOX&ICG achieved a remarkably synergistic anti-cancer effect by the combination of μsPEF and chemotherapy in the tumor-bearing mice model, with the survival time increasing above 90 days without tumor burden. Given that IRE is easily adaptable to different plasma membrane-based vehicles for delivering diverse drugs, this approach could offer a general applicability for cancer treatment.
Electrode materials determine the electrochemical performance of supercapacitors and are strongly affected by their morphologies. In this paper, NiCo2Se4 with three different morphologies, such as ...solid nanoneedle array, hollow nanoneedle array, and nanotube array structure have been in situ grown on carbon cloth by a facile two-step hydrothermal method. The microstructures and electrochemical performance of synthesized integrated electrode material (CC@NiCo2Se4) with different morphologies were studied. It was revealed that the volume of solvent during the selenization process had a significant effect on the morphologies and loading capacity of NiCo2Se4, and the hollow nanoneedle array structure electrode (CC@hn-NiCo2Se4) exhibited the highest specific capacitance of 1687.08 F·g−1 at 2 A·g−1, and 70.64% retention even though the current density was increased to 20 A·g−1. Furthermore, the CC@hn-NiCo2Se4//CC@AC asymmetric supercapacitor exhibited an energy density of 30.71 Wh·kg−1 at 800 W·kg−1. All results highlight that NiCo2Se4 with a hollow nanoneedle array structure will be a promising electrode material for practical supercapacitor applications.
•The evolution of NiCo2Se4 nanoarray morphology was achieved on carbon cloth by a facile two-step hydrothermal method.•The morphology of the NiCo2Se4 nanoarray was controlled by the addition of deionized water.•Asymmetric supercapacitor assembled showed excellent energy storage performance.
The mechanisms of cell death due to electroporation are still not well understood. Recent studies suggest that cell death due to electroporation is not an immediate all-or-nothing response but rather ...a dynamic process that occurs over a prolonged period of time. To investigate whether the dynamics of cell death depends on the pulse parameters or cell lines, we exposed different cell lines to different pulses monopolar millisecond, microsecond, nanosecond, and high-frequency bipolar (HFIRE) and then assessed viability at different times using different viability assays. The dynamics of cell death was observed by changes in metabolic activity and membrane integrity. In addition, regardless of pulse or cell line, the dynamics of cell death was observed only at high electroporation intensities, i.e., high pulse amplitudes and/or pulse number. Considering the dynamics of cell death, the clonogenic assay should remain the preferred viability assay for assessing viability after electroporation.
The rise/fall time of a high-voltage nanosecond pulse affects the application effect of the pulse; therefore, it is of great significance to study the adjustment of the rise/fall time. In this paper, ...a new type of generator topology based on a half-bridge modular multilevel converter (HB-MMC) is proposed that uses MOSFETs as solid-state switches to produce a unipolar/bipolar high-voltage nanosecond pulse with an adjustable rise/fall time. The proposed topology consists of 2 arms, each of which contains several HB-MMC submodules. The capacitors of each arm are charged with a positive voltage and negative voltage in parallel. By controlling the discharging sequence of the two arms, a unipolar or bipolar pulse can be generated. For each arm, by setting the switching sequence of the MOSFETs, the number of capacitors inserted into the discharging circuit can be controlled to allow a multilevel pulse to be generated. The rise/fall time of the output pulse can be adjusted by changing the number of levels and the duration of each level. Detailed illustrations of the proposed configuration and its operational concept are presented. Experimental results for a scaled-down prototype are presented to validate the concept.
Irreversible electroporation (IRE) is a minimally invasive tumor therapy using pulsed electric field with high intensity while the important tissues such as blood vessel, bile duct, and nerve are ...preserved. In addition to ablation area, reversible electroporation (RE) region is also generated using needle electrodes for pulse delivery. The goal of this work is to study the generation of RE region and ablation region on a 2D lung adenocarcinoma cell model in vitro. The tumor model is exposed to electric pulses with various number. The calcium AM and propidium iodide (PI) are examined to detect the ablation area and electroporation area, respectively. The results show that electroporation area firstly tends to plateau after approximately 50 pulses, while the ablation area continues to increase. The percentage of IRE area in total electroporation area increases with additional pulses, which means that RE region could be gradually turned into ablation area with increased pulse number. However, the percentage of IRE area only achieves to 54% for 200 pulses, which indicates that RE region still cannot be completely removed. RE and IRE thresholds appear to converge as the number of pulses increases. An equation between pulse number and the electric field threshold of ablation including the electric field threshold of RE is also provided for lung adenocarcinoma cell ablation. This work may have the value for the optimization of IRE protocols on tumor ablation.
In this work, we proposed nµPEF, a novel pulse configuration combining nanosecond and microsecond pulses (nµPEF), to enhance tumor ablation in irreversible electroporation (IRE) for oncological ...therapy. nµPEF demonstrated improved efficacy in inducing immunogenic cell death, positioning it as a potential candidate for next‐generation ablative therapy. However, the immune response elicited by nµPEF alone was insufficient to effectively suppress distant tumors. To address this limitation, we developed PPR@CM‐PD1, a genetically engineered nanovesicle. PPR@CM‐PD1 employed a polyethylene glycol‐polylactic acid‐glycolic acid (PEG‐PLGA) nanoparticle encapsulating the immune adjuvant imiquimod and coated with a genetically engineered cell membrane expressing programmed cell death protein 1 (PD1). This design allowed PPR@CM‐PD1 to target both the innate immune system through toll‐like receptor 7 (TLR7) agonism and the adaptive immune system through programmed cell death protein 1/programmed cell death‐ligand 1 (PD1/PDL1) checkpoint blockade. In turn, nµPEF facilitated intratumoral infiltration of PPR@CM‐PD1 by modulating the tumor stroma. The combination of nµPEF and PPR@CM‐PD1 generated a potent and systemic antitumor immune response, resulting in remarkable suppression of both nµPEF‐treated and untreated distant tumors (abscopal effects). This interdisciplinary approach presents a promising perspective for oncotherapy and holds great potential for future clinical applications.
The study introduces a groundbreaking pulse configuration termed nµPEF, which synergistically employs nanosecond and microsecond pulses to trigger cancer cell death with an immunogenic pattern. Furthermore, by integrating nanoenabled immunomodulation, nµPEF amplifies the systemic immune response and curbs the development of secondary tumors, thus presenting a novel outlook for oncological therapy.
This paper introduces unipolar high-frequency nanosecond pulse bursts, which combine the advantages of microsecond pulsed electric fields and nanosecond pulsed electric fields, for the treatment of ...tumors. To take full advantage of this nonthermal pulsed electric field treatment, it is necessary to study the thermal effects of the high-electric-field nanosecond pulse bursts inside tumor tissue. A multiparametric analysis is performed based on a finite-element model of skin with a melanoma tumor that is nipped using the Tweezertrodes. The electric field ranges from 1 to 10 kV/cm, the pulsewidth ranges from 50 to 500 ns, and the frequency in the pulse bursts ranges between 100 kHz and 1 MHz. The total pulselength is <inline-formula> <tex-math notation="LaTeX">100~\mu \text{s} </tex-math></inline-formula>, and the frequency of the pulse bursts is 1 Hz. The Pennes bioheat transfer equation and the Arrhenius equation are used to calculate the temperature and the thermal damage. For pulse parameters of 5 kV/cm, 500 ns, and 1 MHz, the simulated temperature of the skin tumor is only 37.48 °C after 1 s, and the thermal damage is negligible. The temperature and thermal damage to the melanoma tumor in the skin are simulated and calculated for various electric fields, pulse widths, and frequencies. The relationship between the thermal effects on the tumor and the pulse parameters is researched, and pulse parameters for a tumor without thermal damage are ascertained. Temperature measurements of melanoma tumors in nude mice in vivo show that the change in experimental temperature in the tumors is consistent with the simulated average tumor temperature.
Magnetic pulse compression (MPC) systems are suitable for generating (Dielectric Barrier Discharges) DBD owing to their capability for producing high amplitude, short pulse voltage waves. Because of ...the frequency limit caused by magnetic core reset, and by the high DBD discharge voltage, which is often up to several tens kV under the low-frequency unipolar voltage wave, this paper proposes a high frequency, bipolar magnetic compression system to study MPC discharge characteristics. First, the principle of bipolar MPC is explained, which is based on full bridge inverter circuit, pulse transformer, and magnetic switch. Additionally, the design of the pulse transformer and magnetic switch are described. Then, the waveform of the resistive load is tested and compared with PSpice simulation results. It was found that the nanosecond pulse generator produces a pulse on a resistor with an amplitude of 0-13 kV, a rise time of approximately 100ns, a repetition frequency of 0 to several kHz. The preliminary experimental data show the effects of repetition frequency on discharge characteristics. The successful development of the system will facilitate deeply study on bipolar high frequency DBD discharge.
Prediction of the biodegradability of organic pollutants is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. In this paper,stepwise ...multiple linear regression analysis method was applied to establish quantitative structure biodegradability relationship（QSBR） between the chemical structure and a novel biodegradation activity index（qmax） of 20 polycyclic aromatic hydrocarbons（PAHs）. The frequency B3LYP/6-311＋G（2df,p） calculations showed no imaginary values, implying that all the structures are minima on the potential energy surface. After eliminating the parameters which had low related coefficient with qmax, the major descriptors influencing the biodegradation activity were screened to be Freq, D, MR, EHOMOand To IE. The evaluation of the developed QSBR mode, using a leave-one-out cross-validation procedure, showed that the relationships are significant and the model had good robustness and predictive ability. The results would be helpful for understanding the mechanisms governing biodegradation at the molecular level.
Based on a global input-output model, this paper investigates the CO2 emission transfer between China and developed economies through trade. The results show that approximately 15-23 percent of ...China＇s production-based emissions during 1995-2009 were induced by the production of goods and services satisfying final demand in developed economies. Decomposition of emission transfers shows that trade of intermediate products played a significant role in emission transfer from developed economies to China. Most developed economies have consumption-based emission responsibilities that are higher than their production-based responsibilities, whereas China＇s consumption-based responsibility is significantly lower than its production-based responsibility. We argue that a fair and efficient carbon accounting approach should take CO 2 emission transfers from developed economies to developing economies into consideration. It is important that China and its developed trade partners cooperate in reducing emission transfers.
