Destruction Technology Research Articles

"PFH/AGM-CBA/HSV-TK/LIPOSOME-Affibody": Novel Targeted Nano Ultrasound Contrast Agents for Ultrasound Imaging and Inhibited the Growth of ErbB2-Overexpressing Gastric Cancer Cells.

ObjectiveGastric cancer is one of the most lethal malignancies in the world. However, the current research on the diagnosis and treatment of nano-ultrasound contrast agents in the field of tumor is mostly focused on breast cancer, ovarian cancer, prostate cancer, liver cancer, etc. Due to the interference of gas in the stomach, there is no report on the treatment of gastric cancer. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) therapy system is the most mature tumor suicide gene in cancer treatment. At the same time, in order to improve its safety and efficiency, we designed a gastric tumor targeted ultrasound-triggered phase-transition nano ultrasound contrast agent PFH/AGM-CBA/HSV-TK/Liposome (PAHL)-Affibody complex.MethodsIn our study, guanidinylated SS-PAAs polymer poly(agmatine/N, N′-cystamine-bis-acrylamide) (AGM-CBA) was used as a nuclear localization vector of suicide gene to form a polyplex, perfluorohexane (PFH) was used as ultrasound contrast agent, liposomes were used to encapsulate perfluorohexane droplets and the polyplexes of AGM-CBA/HSV-TK, and affibody molecules were conjugated to the prepared PAHL in order to obtain a specific targeting affinity to human epidermal growth factor receptor type 2 (ErbB2) at gastric cancer cells. With the aid of ultrasound targeted microbubble destruction technology and the nuclear localization effect of AGM-CBA vector, the transfection efficiency of the suicide gene in gastric cancer cells was significantly increased, leading to significant apoptosis of gastric cancer cells.ResultsIt was shown that PAHL-Affibody complex was nearly spherical with an average diameter of 560 ± 28.9 nm, having higher and specific affinity to ErbB2 (+) gastric cells. In vitro experiments further confirmed that PAHL could target gastric cancer cells expressing ErbB2. In a contrast-enhanced ultrasound scanning study, the prepared ultrasound-triggered phase-change nano-ultrasound contrast agent, PAHL, showed improved ultrasound enhancement effects. With the application of the low-frequency ultrasound, the gene transfection efficiency of PAHL was significantly improved, thereby inducing significant apoptosis in gastric cancer cells.ConclusionThis study constructs PFH/AGM-CBA/HSV-TK/Liposome-Affibody nano ultrasound contrast agent, which provides new ideas for the treatment strategy of ErbB2-positive gastric cancer and provides some preliminary experimental basis for its inhibitory effect.

(Invited) Electrical Discharge Plasma Technology for the Treatment of Fab Wastewater

This work investigates plasma-assisted degradation of triflate and perfluorobutane sulfonate (PFBS), two short-chained per- and polyfluoroalkyl substances (PFAS) regularly found in the effluents of semiconductor fabrication processes. Recent studies have shown that triflate and PFBS are persistent in the environment and associated with negative health impacts. Here, the degradation of short-chain PFAS was investigated using a point-ring plasma reactor electrode configuration in which plasma is formed in argon gas and is contacting the surface of contaminated water. Experiments were first carried out in lab-prepared solutions and subsequently in a fab effluent membrane concentrate containing dozens of long- and short-chain PFAS. Time-dependent concentration profiles for PFAS were followed for a range of operational parameters and degradation byproducts identified and when possible quantified.Results indicate that the removal rates of short-chain PFAS are significantly lower than those of their long-chain counterparts due to their inability to accumulate and concentrate at gas-liquid interfaces. The addition of cetyltrimethylammonium bromide (CTAB), a cationic surfactant, significantly improved degradation rates of short-chained PFAS in lab-prepared solutions by transporting them to the plasma-liquid interface, the region of chemical reactivity. Experiments conducted with different surfactant types revealed that only cationic surfactants such as CTAB affect PFBS degradation, mainly through electrostatic attraction. In fab wastewater, the CTAB-PFAS binding may be hindered by the presence of different PFAS and CTAB may be competing with long-chain PFAS for the sites at the plasma-liquid interface. Nevertheless, through careful process design one can achieve near-complete destruction of the majority of PFAS allowing the electrical discharge plasma process to maintain its position as the leading PFAS destruction technology.

A novel cryogenic condensation system based on heat-driven refrigerator without power input for volatile organic compounds recovery

Volatile organic compounds (VOCs) are important precursors of pollutants such as PM2.5 and ozone, and the development of their treatment technologies is of great significance to environmental protection and economic development. The current VOCs destruction technology, such as the combustion method, has low operating costs, but there is a large waste in the treatment of high-value gas; while the current VOCs recovery technology, such as the condensation method based on refrigerator cooling, can recover high-value gas, but it still has some unsatisfactory aspects in terms of emission concentration, refrigerant use, and power supply. In this paper, a novel cryogenic condensation system based on a heat-driven refrigerator without power input for oil gas VOCs recovery was proposed. The heat obtained by burning part of the oil gas VOCs is employed to drive a thermoacoustic refrigerator using helium as working gas to realize the recovery of the remaining oil gas VOCs, which has the advantages of not relying on external power supply, using natural working fluid, and zero-emission of oil gas. A thermodynamic calculation model was established to quantitatively calculate the recovery efficiency. The results show that the remaining 91.0% of the oil gas VOCs can be recovered by burning 9.0% of the oil gas VOCs when the refrigeration temperature is 200 K, the heat source temperature is 873 K and the concentration is 33.5% at 100 kPa. And compared with the method of burning part of the liquefied VOCs, the method of burning part of inlet gaseous VOCs to drive the refrigerator has a higher recovery efficiency (around 10%). The effects of the refrigeration temperature, the heat source temperature, VOCs concentration, VOCs inlet pressure, and refrigerator efficiency on the system were also analyzed.

Visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system against immune-associated nephropathy without glucocorticoid side effect.

Glucocorticoids are widely used in the treatment of nephritis, however, its dose-dependent side effects, such as the increased risk of infection and metabolic disturbances, hamper its clinical use. This study reports a visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system (named as Dex/PFP@LIPs-BMS-α), which specific delivers dexamethasone (Dex) to podocyte targets and reduces systemic side effects.Methods: The glucocorticoid nano-delivery system was synthesized by a lipid thin film and a simple facile acoustic-emulsification method. This glucocorticoid nano-delivery system used BMS-470539 (BMS-α), a synthetic compound, as a “navigator” to specifically identify and target the melanocortin-1 receptor (MC-1R) on podocytes. The loaded perfluoropentane (PFP) realizes the directed "explosion effect" through ultrasound-targeted microbubble destruction (UTMD) technology under the coordination of low intensity focused ultrasound (LIFU) to completely release Dex.Results: Both in vitro and in vivo experiments have demonstrated that Dex/PFP@LIPs-BMs-α accurately gathered to podocyte targets and improved podocyte morphology. Moreover, in vivo, proteinuria and serum creatinine levels were significantly reduced in the group treated with Dex/PFP@LIPs-BMS-α, and no severe side effects were detected. Furthermore, Dex/PFP@LIPs-BMS-α, with capabilities of ultrasound, photoacoustic and fluorescence imaging, provided individualized visual guidance and the monitoring of treatment.Conclusion: This study provides a promising strategy of Dex/PFP@LIPs-BMS-α as effective and safe against immune-associated nephropathy.

Downregulation of GSK-3β Expression via Ultrasound-Targeted Microbubble Destruction Enhances Atherosclerotic Plaque Stability in New Zealand Rabbits

Accumulating evidence suggests that atherosclerosis (AS) is the underlying cause of vascular diseases, including heart disease and stroke. Ultrasound-targeted microbubble destruction (UTMD) technology provides a tolerable, efficient and effective system for drug delivery and gene transfection, which has broad application prospects in the treatment of AS. In addition, glycogen synthase kinase (GSK)-3β has been implicated as a potentially valuable therapeutic agent for AS treatment; however, the specific molecular mechanisms remain unknown. Therefore, this study was conducted to explore the effect of downregulation of GSK-3β expression via UTMD on atherosclerotic plaque stability. We established a THP-1 macrophage-derived foam cell model in vitro and an atherosclerotic plaque model in the right common carotid artery of New Zealand rabbits. We determined levels of the relevant vulnerable plaque stability elements. The results indicate that GSK-3β was upregulated in the foam cells and in atherosclerotic rabbits. Downregulation of GSK-3β expression by UTMD suppressed vulnerable plaque factors and inflammation in vitro and in vivo, changed the cytoskeleton of the foam cells in vitro, increased Young's modulus and decreased the peak intensity of atherosclerotic plaque in vivo. Moreover, GSK-3β inhibition by UTMD did not influence the viability of the foam cells. Collectively, our results indicate that GSK-3β could be a potential target for anti-atherogenic interventions and, in particular, can improve the stability of AS plaques in combination with UTMD.

Ultrasound-enhanced fluorescence imaging and chemotherapy of multidrug-resistant tumors using multifunctional dendrimer/carbon dot nanohybrids

Development of innovative nanomedicine enabling enhanced theranostics of multidrug-resistant (MDR) tumors remains to be challenging. Herein, we report the development of a newly designed multifunctional yellow-fluorescent carbon dot (y-CD)/dendrimer nanohybrids as a platform for ultrasound (US)-enhanced fluorescence imaging and chemotherapy of MDR tumors. Generation 5 (G5) poly(amidoamine) dendrimers covalently modified with efflux inhibitor of d-α-tocopheryl polyethylene glycol 1000 succinate (G5-TPGS) were complexed with one-step hydrothermally synthesized y-CDs via electrostatic interaction. The formed G5-TPGS@y-CDs complexes were then physically loaded with anticancer drug doxorubicin (DOX) to generate (G5-TPGS@y-CDs)-DOX complexes. The developed nanohybrids display a high drug loading efficiency (40.7%), strong y-CD-induced fluorescence emission, and tumor microenvironment pH-preferred DOX release profile. Attributing to the DOX/TPGS dual drug design, the (G5-TPGS@y-CDs)-DOX complexes can overcome the multidrug resistance (MDR) of cancer cells and effectively inhibit the growth of cancer cells and tumors. Furthermore, the introduction of US-targeted microbubble destruction technology was proven to render the complexes with enhanced intracellular uptake and anticancer efficacy in vitro and improved chemotherapeutic efficacy and fluorescence imaging of tumors in vivo due to the produced sonoporation effect. The developed multifunctional dendrimer/CD nanohybrids may represent an advanced design of nanomedicine for US-enhanced theranostics of different types of MDR tumors.

Synergistic Anti-tumor Mechanisms of Low-frequency Ultrasound-targeted Microbubble Destruction:Mechanisms and Application

Ultrasound contrast agent microbubbles combined with low frequency ultrasound named as low-frequency ultrasound-targeted microbubble destruction technology has become an effective and non-invasive anti-tumor therapy for deep tumors.It can enhance the efficacies of chemotherapy,gene therapy,immunotherapy,and anti-angiogenic therapy by improving cell membrane permeability and destroying tumor neovasculature.It can be applied to sonodynamic therapy and realize multimodal synergistic therapy on the basis of nanoparticles,which increases the anti-tumor efficiency and offers a promising target therapy for tumors.

Phosphorus dendrimer-based copper(II) complexes enable ultrasound-enhanced tumor theranostics

Abstract Design of simple-component theranostic agents with enhanced tumor accumulation represents a novel strategy in the area of precision nanomedicine for effective tumor theranostics. Herein, we report an innovative theranostic strategy based on ultrasound-enhanced tumor accumulation of a theranostic agent of phosphorus dendrimer-copper(II) complexes (1G3-Cu). The employed 1G3-Cu complexes represent a drug-free nanotheranostic agent with a simple composition possessing an r1 relaxivity of 0.7024 mM−1 s−1 for T1-weighted magnetic resonance (MR) imaging and an IC50 of 1.24 μM to inhibit the growth of a pancreatic cancer cell line. We show that cancer cells can be inhibited by the 1G3-Cu complexes through the activation of the apoptotic process with the upregulation of Bax, P53 and PTEN, downregulation of Bcl-2, and decrease of intracellular ATP. With the assistance of ultrasound targeted microbubble destruction (UTMD) technology that can increase cell membrane permeability temporarily via sonoporation effect, the 1G3-Cu complexes enable enhanced tumor MR imaging and chemotherapy due to their improved tumor accumulation. With the proven minimal toxicity to normal tissues at imaging and therapeutic doses, the prepared 1G3-Cu complexes may be potentially employed for UTMD-enhanced theranostics of different types of cancer.

A novel UTMD system facilitating nucleic acid delivery into MDA-MB-231 cells.

Gene therapy is emerging as a promising method for the treatment of various diseases. The safe and efficient delivery of therapeutic nucleic acids is a gene therapy prerequisite. Ultrasound, particularly in combination with microbubbles composed of biocompatible materials such as lipid, PLGA and chitosan, is a novel non-viral tool for gene transportation. Under ultrasound irradiation, microbubbles explode and generate pores in the cell membrane. Hence, genes can enter cells more easily. In order to transfect nucleic acids into MDA-MB-231 cells in a low-cost and non-viral manner for further breast cancer gene therapy studies, we explored ultrasound targeted microbubble destruction (UTMD) technology and evaluated the efficiency and safety of the delivery of plasmid encoding enhanced green fluorescent protein (pEGFP) and a microRNA-34a (miR-34a) mimic by UTMD. Sonovitro ultrasonic apparatus was employed to generate ultrasonic field, which was developed by our group. Ultrasonic parameters, including acoustic intensity (AI), exposure time (ET) and duty cycle (DC), were optimized at 0.6 W/cm2 AI, 20 s ET and 20% DC, the cell viability was not obviously impaired. Under these conditions, the UTMD-mediated transfection efficiency of pEGFP was greater than 40%. In addition to plasmid DNA, an miR-34a mimic was also successfully introduced into the cytoplasm by UTMD and found to inhibit proliferation, induce apoptosis of MDA-MB-231 cells and regulate downstream molecules. The present study indicates that further in vivo UTMD-mediated gene therapy studies are warranted.

Assessment of Heavy Metal Contamination in the Soil of Al-Muthanna Storage Site using Geospatial techniques

During the early 90s, military operations and United Nations Special Commission “UNSCOM” teams have destroyed the Iraqi past chemical program. Both operations led to a large number of scattered remnants of contaminated areas. The quantities of hazardous materials, incompletely destructed materials and toxic chemicals were sealed in two bunkers. Lack of appropriate destruction technology led to the spread of contamination around the storage area. This paper aims to introduce the environmental assessment of the hazard contamination in the storage site area using Geomatics analysis technique. The environmental assessment for contamination level of eight main chemical compounds (Chromium Cr, Phosphate PO4, Nitrate NO3, Cadmium Cd, Copper Cu, Nickel Ni, Zinc Zn and Lead Pb) have been assessed and analyzed. Soil samples taken from the grid on the site and its surrounding areas have been investigated and analyzed compared to the reference points. The storage area grid was divided into 30 major sectors. 10 samples from each sector were acquired and evaluated. The assessment results indicated that Cr level exceeded the permitted level by (180) times, PO4 level exceeded the permitted level by (35) times, Cu by (1050) times over the permitted level and Ni level exceeds the permitted level over by (50) times. Activity level of Zn in the soil samples of the study area also exhibits large variability with (16000) times over the permitted level on the surrounding isolation protection on the north-west Wall. Very high Contamination spot activity of Pb was found in Destruction zone, about (1350) times over the background level. There is no activity detected for the Cadmium and Nitrate in the storage area site.

Detection of Nutrients and Major Ions at Al Muthanna Storage Site Soil

In the early 90s military operations and United Nations Special Commission “UNSCOM” teams have been destroyed the past Iraqi chemical program. Both operations led an extensive number of scattered remnants of contaminated areas. The quantities of hazardous materials, incomplete destructed materials, and toxic chemicals were sealed in two bunkers. Deficiency of appropriate destruction technology led to spreading the contamination around the storage site. This paper aims to introduce the environmental detection of the contamination in the storage site area using geospatial analysis technique. The environmental contamination level of nutrients and major ions such as sulphate (SO4), potassium (K), sodium (Na), magnesium (Mg), calcium (Ca), chlorine (Cl), phosphate (PO4) and nitrate (NO3) were detected and analyzed. The grid soil samples on the site and surrounding areas have been investigated, analyzed, and compared to the background points. The storage area grid was divided into 30 major sectors and all samples were evaluated from acquires 10 samples from each sector. The detection results have indicated that SO4 level was exceeded the permitted level by 25 times, K level also exceeded the permitted level but by 460, Na ions were 85 times greater the permitted level. Mg level was 180 times higher than that of permitted content. Activity level of Ca in the soil samples of the study area has also exhibited variability with nine times over the permitted level near the bunkers. However, very high contamination spot activity of Cl was found in destruction zone about which 44 times over the background level was found while PO4 level exceeded the permitted level by 35 times over the permitted level and there was no activity detected for the nitrate in the storage area site.

Toxic Soil Contamination in Al Muthanna Storage Site Using Geospatial Analysis Technique

The Iraqi past chemical program was destroyed by the military operations or destructed by the UNSCOM/CDG teams during the early 90s. Both operations lead to a large number of scattered remnants of contaminated areas. The quantities of hazardous materials, incomplete destructed materials and toxic chemicals were sealed in two well-protected bunkers. Lack of appropriate destruction technology, led to spread the contamination around the bunkers .since 2009 the Iraqi experts have been working to develop a practical plan for decommissioning the contaminated area. This paper introduces the hazard contamination in the storage site using geospatial analysis technique. The contamination level of two main chemical compounds (Copper Cu and cyanide Cn) have been evaluated and analyzed, taken from different soil samples of the site, surrounding areas have investigated and analyzed compared to the reference points. The storage area divided into 30 sector major sectors level of soil samples from soil surface all samples collected from acquires 10 samples from each sector. The results showed The Cn level exceeds the permitted level by (55000) times and for copper by (1050) times over the permitted level very high Contamination activity was found in the storage area.

О возможности создания технологии “взрывного” разрушения массива горных пород – диэлектриков направленным электромагнитным потоком концентрированной энергии СВЧ.

О возможности создания технологии “взрывного” разрушения массива горных пород – диэлектриков направленным электромагнитным потоком концентрированной энергии СВЧ.

Targeted delivery of reduced graphene oxide nanosheets using multifunctional ultrasound nanobubbles for visualization and enhanced photothermal therapy.

Ultrasound molecular imaging as a promising strategy, which involved the use of molecularly targeted contrast agents, combined the advantages of contrast-enhanced ultrasound with the photothermal effect of reduced graphene oxide (rGO).Methods and resultsThe heparin sulfate proteoglycan glypican-3 (GPC3) is a potential molecular target for hepatocellular carcinoma (HCC). In this study, we covalently linked biotinylated GPC3 antibody to PEGylated nano-rGO to obtain GPC3-modified rGO-PEG (rGO-GPC3), and then combined rGO-GPC3 with avidinylated nanobubbles (NBs) using biotin-avidin system to prepare NBs-GPC3-rGO with photothermal effect and dispersibility, solubility in physiological environment. The average size of NBs-GPC3-rGO complex was 700.4±52.9 nm due to the polymerization of biotin-avidin system. Scanning electron microscope (SEM) showed NBs-GPC3-rGO attached to human hepatocellular carcinoma HepG2 cell. The ultrasound-targeted nanobubble destruction (UTND) technology make use of the physical energy of ultrasound exposure for the improvement of rGO delivery. Compared with other control groups, the highest nanobubble destruction efficiency of NBs-GPC3-rGO was attributed to the dissection effect of rGO on UTND. This is a positive feedback effect that leads to an increase in the concentration of rGO around the HepG2 cell. So NBs-GPC3-rGO using UTND and near-infrared (NIR) irradiation resulted in cell viability within 24 h, 48 h, 72 h lower than other treatment groups.ConclusionThis work established NBs-GPC3-rGO as an ultrasonic photothermal agent due to its suitable size, imaging capability, photothermal efficiency for visual photothermal therapy in vitro.

A new mud-pulse rocks destruction technology is a prospect to the effective earth reclamation

A comparative analysis of the mud-pulse destruction efficiency of tough and sharp rocks in the ore industry relatively to the existing drilling and blasting technology, as well as the testing destruction processes by hypersonic steel and hollow charge projectiles is provided in the article. The reasoned explanations of the compared processes of the hypersonic projectiles introduction into the solid and the character of the volumetric breaking are given. The features of technical, social and economic efficiency of mud-pulse technology are listed in the mode of hypersonic interaction with the destroyed solid. The method and design of environmentally sound electric-discharge drive for mud-pulse devices primarily constructed for the strong rocks destruction is described. This method is demonstrated to involve rapid overheating of a part of weak electrolyte (for example, salted water) by a powerful electric discharge and the following water discharge under the extreme pressure of the vapor-ionic substance on the tail section of the water charge. The new forceful electric discharge drive is the major unit in the complex of highly effective and environmentally sound rock-destructing mechanism operating in the flow line mode when cavern excavations. Alongside, the article provides experimental design of a mud-pulse rock-destruction device is the current model of a new drilling tool for the large-diameter gasification wells sinking along the coal beds with the inclusion of a large number of rock formations with an impulse striking power of up to 25 kJ. The results of laboratory tests are provided. The received data and characteristics of the units and model parts operation will be used to create industrial samples of the new equipment.

Apatinib-loaded lipid nanobubbles combined with ultrasound-targeted nanobubble destruction for synergistic treatment of HepG2 cells in vitro

PurposeApatinib, an oral small-molecule antiangiogenetic medicine, is used to treat patients with advanced hepatocellular carcinoma. However, its systemic toxic side effects cannot be ignored. The ultrasound (US)-targeted nanobubble destruction technology can minimize systemic drug exposure and maximize therapeutic efficacy. The aim of this study was to develop novel GPC3-targeted and drug-loaded nanobubbles (NBs) and further assess the associated therapeutic effects on hepatocellular carcinoma cells in vitro.Materials and methodsApatinib-loaded NBs were prepared by a mechanical vibration method. GPC3, a liver tumor homing peptide, was coated onto the surface of apatinib-loaded NBs through biotin–avidin interactions to target liver cancer HepG2 cells. The effects of different treatment groups on cell proliferation, cell cycle, and apoptosis of HepG2 cells were tested.ResultsThe NBs could achieve 68% of optimal drug encapsulation. In addition, ligand binding assays demonstrated that attachment of targeted NBs to human HepG2 liver cancer cells was highly efficient. Furthermore, cell proliferation assays indicated that the antiproliferative activities of GPC3-targeted and apatinib-loaded NBs in combination with US (1 MHz, 1 W/cm2, 30 s) were, respectively, 44.11%±2.84%, 57.09%±6.38%, and 67.51%±2.89% after 24, 48, and 72 h of treatment. Treatment with GPC3-targeted and apatinib-loaded NBs also resulted in a higher proportion of cells in the G1 phase compared with other treatment groups such as apatinib only and nontargeted apatinib-loaded NBs when US was utilized.ConclusionUS-targeted and drug-loaded nanobubble destruction successfully achieved selective growth inhibition and apoptosis in HepG2 cells in vitro. Therefore, GPC3-targeted and apatinib-loaded NBs can be considered a novel chemotherapeutic approach for treating liver cancer in combination with US.

Chitosan-conjugated lipid microbubble combined with ultrasound for efficient gene transfection

ABSTRACTNon-viral vectors, as gene carriers, have advantages of biological safety and cost-efficiency over viral vectors. However, low transfection efficiency hampers their further clinical application. In this study, we developed a novel chitosan-conjugated lipid microbubble (CMB), which has good biocompatibility and high gene loading capacity. By ultrasound-targeted microbubble destruction (UTMD) technology, plasmid DNA could be efficiently delivered into HEK293T cells. The parameters for UTMD including acoustic intensity (AI), duty cycle (DC), exposure time (ET) and microbubble concentration were systematically optimised. Under the optimal conditions (AI, 1.0 W/cm2; DC, 10%; ET, 60 s; 10% CMBs), the gene transfection efficiency was significantly enhanced, without obvious impairment of the cell viability (over 80%). This study described a novel gene transfection strategy that combines CMBs with ultrasound to facilitate safe and efficient gene transfection in vitro with the potential for in vivo targeted gene delivery.

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer

To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for PDT, while amino groups could adsorb siRNA through electrostatic interaction for FOXA1 KD, which could inhibit the proliferation of estrogen-dependent ER+ BC. This system showed high photosensitizer and gene loading content. Moreover, CpMBs/siRNA can be converted into nanoparticles with low-frequency pulsed ultrasound (LFUS) exposure, which increase the transfection efficiency of siRNA (∼4 fold) and the porphyrin uptake (∼8 fold) in MCF-7 (a human breast cancer cell line, ER+) by sonoporation effect. In vivo, UTMD was performed under the guidance of CEUS, and the fluorescence intensity of CpMBs/siRNA at the tumour site reached a peak value at 6 h after injection and it was retained in the following 24 h. Furthermore, there was no tumour recurrence during the observation period (21 days) in the group of PDT combined with FXOA1 KD. Compared to the PDT or FOXA1 KD alone group, the combination of these two methods was much more efficient in inhibiting ER+ breast cancer, showing a good synergistic effect. CpMBs/siRNA combined with UTMD dramatically increased the local accumulation of porphyrin and siRNA through ultrasound-induced sonoporation effect under the guidance of CEUS, showing excellent therapeutic effect for estrogen-dependent ER+ breast cancer.

Formation of brominated and chlorinated dioxins and its prevention during a pilot test of mechanochemical treatment of PCB and PBDE contaminated soil.

The destruction of persistent organic pollutants (POPs) is a large challenge in particular in developing and emerging economies. To date, a detailed assessment of non-combustion technologies with respect to formation of dioxins is lacking. In this study, an assessment of mechanochemical (MC) destruction technology for polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in contaminated soil remediation was conducted. Actual applied conditions of pilot-scale MC POPs destruction process indicates that the temperature increase inside the ball mills has the potential to form high levels of toxic polybrominated and polychlorinated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) when dioxin precursors are present. Therefore, the MC technology was modified for treatment of the PCB and PBDE containing soil including an efficient cooling system which could prevent the formation of PXDD/F during the destruction of PCBs and PBDEs. This is likely relevant for all contaminated soils containing relevant dioxin precursor and need to be considered for treatment of soils with MC and probably other non-combustion technologies. Graphical abstract ᅟ.

Novel cell-penetrating peptide-loaded nanobubbles synergized with ultrasound irradiation enhance EGFR siRNA delivery for triple negative Breast cancer therapy

The lack of safe and effective gene delivery strategies remains a bottleneck for cancer gene therapy. Here, we describe the synthesis, characterization, and application of cell-penetrating peptide (CPP)-loaded nanobubbles (NBs), which are characterized by their safety, strong penetrating power and high gene loading capability for gene delivery. An epidermal growth factor receptor (EGFR)-targeted small interfering RNA (siEGFR) was transfected into triple negative breast cancer (TNBC) cells via prepared CPP-NBs synergized with ultrasound-targeted microbubble destruction (UTMD) technology. Fluorescence microscopy showed that siEGFR and CPP were loaded on the shells of the NBs. The transfection efficiency and cell proliferation levels were evaluated by FACS and MTT assays, respectively. In addition, in vivo experiments showed that the expression of EGFR mRNA and protein could be efficiently downregulated and that the growth of a xenograft tumor derived from TNBC cells could be inhibited. Our results indicate that CPP-NBs carrying siEGFR could potentially be used as a promising non-viral gene vector that can be synergized with UTMD technology for efficient TNBC therapy.