ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Yan Chen,Yangbiao Liang,Peng Jiang,Fei Li,Bo Yu,Fei Yan
Microbubbles (MBs) have recently emerged as promising theranostic carriers for ultrasound contrast imaging and drug delivery. However, conventional lipid-based MBs have a poor drug encapsulation efficiency, and polymer-based MBs show a weak capability in contrast imaging and ultrasound-triggered drug release. Here, we developed a novel type of multiporous lipid/PLGA hybrid MBs (lipid/PLGA MBs) that solved the dilemma of MBs as imaging agents and drug carriers. The lipid/PLGA MBs were designed through regulating the elasticity of the bubble shells using lipids to incorporate into the PLGA shells and ammonium bicarbonate as a gas-generating agent. The softened shells and the porous bubble structure make them be able to generate stronger harmonic signals and be more vulnerable to ultrasound irradiation, leading to their excellent performance in ultrasound contrast imaging and ultrasound-triggered MB destruction in vitro and in vivo. By using doxorubicin (Dox) as a model drug, the Dox-loaded lipid/PLGA MBs (Dox-lipid/PLGA MBs) were prepared and achieved a high drug encapsulation efficiency. The real-time tracking of drug delivery and on-command controlled drug release by ultrasound were successfully realized in the tumor-bearing mice. A significantly enhanced tumor growth inhibition effect could be observed when using Dox-lipid/PLGA MBs combined with ultrasound irradiation, compared with free Dox and Dox-lipid/PLGA MBs without ultrasound. Our study provides an innovative multifunctional platform of MBs for ultrasound contrast imaging and drug delivery applications.
研究领域:
医学影像学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Minerals
·
2021
·Vol. 11
·期 10
·1079
·
IF 2.644
Penggang Wei,Liuyi Ren,Yimin Zhang,Shenxu Bao
The recovery of fine wolframite is low when using traditional flotation that does not use a microbubble. In this study, a microbubble was introduced into the fine wolframite flotation system; −20 μm wolframite was used as an experiment sample and octyl hydroxamic acid as the collector. The recovery of microbubble flotation reached 84.07%, which is about 12.04% higher than that of traditional flotation. A single-factor flotation experiment, high-speed camera analysis, and SEM (Scanning Electron Microscopy) analysis were used to study the influence of microbubbles on the flotation of fine wolframite. The results show that fine wolframite will more easily agglomerate under the action of microbubbles. The octyl hydroxamic acid adsorbed on the surface of wolframite treated with microbubbles is denser and more abundant.Keywords:wolframite;fine particles;microbubble;flotation
研究领域:
矿物加工工程
·
化学工程
✓ 已验证
DOI
高影响因子
TUMOR BIOLOGY
·
2016
·Vol. 37
·期 7
·8609-8619
·
IF 2.926
Xu Jinfeng,Zeng Xinxin,Liu Yingying,Luo Hui,Wei Zhanghong,Liu Huiyu,Zhou Yuli,Zheng Hairong,Zhou Jie,Tan Guanghong,Yan Fei
Ultrasound-targeted microbubble destruction (UTMD) has become a novel gene/drug delivery method in cancer therapeutic application. However, the gene transfection efficiency mediated by UTMD is still unsatisfactory. Here, we introduced iRGD/CCR2 dual-targeted cationic microbubbles (MB iRGD/CCR2 ) which was modified with PEI-600 and coated with iRGD peptides and anti-CCR-2 antibodies. It showed that MB iRGD/CCR2 had a 25.83 ± 1.57 mV surface zeta potential and good stability. The experiments in vitro showed MB iRGD/CCR2 had higher binding efficiency with both bEnd.3 cells and MCF-7 cells than that of iRGD or CCR2 single-targeted cationic microbubbles (MB iRGD or MB CCR2 ) ( P < 0.05 for both). Agarose gel electrophoresis assay showed that MB iRGD/CCR2 can effectively load pGPU6/GFP/Neo-shAKT2 plasmid DNA. Compared with the plain MBs (MB control ) or single-targeted cationic MBs including MB iRGD and MB CCR2 ( P < 0.05 for all), the dual-targeted cationic MB iRGD/CCR2 groups had higher gene transfection efficiency under US exposure. It showed that the dual-targeted cationic MB iRGD/CCR2 has a potential value to be used as an ultrasound imaging probe for ultrasound image-guided tumor gene therapy.
研究领域:
医学影像
·
基因治疗
·
癌症研究
·
超声技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cellular and Molecular Bioengineering
·
2019
·Vol. 13
·期 1
·99-112
·
IF 2.477
Wang Yue,Li Xiaoli,Liu Lanlan,Liu Bingruo,Wang Feng,Chen Changsheng
Introduction Ultrasound-targeted microbubble destruction (UTMD) has been shown a promising approach for target-specific gene delivery and treatment of many diseases in the past decade. To improve the therapeutic potential of UTMD, the gene carrier of microbubbles should possess adequate DNA condensation capability and (or) specific cell or tissue selectivity. The tissue-targeted and ultrasound-targeted cationic microbubbles were developed to meet gene therapy. Methods A tissue-targeted stearic acid-inserted cationic microbubbles (SCMBs) were prepared for ultrasound-targeted gene delivery. Branched PEI was modified with stearic acid and further mixed with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and biot-1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N -[methoxy (polyethylene glycol)-2000] (ammonium salt) (Biot-DSPE-PEG2000), intercellular adhesion molecule-1 (ICAM-1) antibody and plasmid DNA to prepare cationic microbubbles through ultrasonic hydration. The ICAM-1 antibody and plasmid DNA were expected to assemble to the surface of SCMBs via biotin-avidin interaction and electrostatic interaction, respectively. Results It was found that the SCMBs had higher zeta potential compared with neutral microbubbles (NMBs) and cationic microbubbles (CMBs). In contrast, DNA incorporated SCMBs4 showed negative potential, exhibiting good DNA-binding capacity. Confocal images showed that the HeLa cells were attached around by the SCMBs4 from the view of green fluorescence of fluorescein isothiocyanate-loaded IgG which conjugated to ICAM-1 antibody on their surface. After ultrasound treatment, HeLa cells treated with SCMBs exhibited slightly stronger red fluorescence under confocal laser scanning microscope, indicating a synergistic promotion for transfection efficiency. Conclusions This tissue- and ultrasound-targeted cationic microbubble demonstrated here showed a promising strategy for improving gene therapy in the future.
研究领域:
生物医学工程
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Wang Feng,Dong Lei,Wei Xixi,Wang Yongling,Chang Liansheng,Wu Hongwei,Liu Shuyuan,Chang Yuqiao,Yin Yaling,Luo Xiaoqiu,Jia Xiaojian,Yan Fei,Li Nana
Gambogic acid (GA) is a highly effective antitumor agent, and it is used for the treatment of a wide range of cancers. It is challenging to deliver drugs to the central nervous system due to the inability of GA to cross the blood–brain barrier (BBB). Studies have shown that ultrasound-targeted microbubble destruction can be used for transient and reversible BBB disruption, significantly facilitating intracerebral drug delivery. We first prepared GA–loaded porous-lipid microbubbles (GA porous-lipid/PLGA MBs), and an in vitro BBB model was established. The cell viability was detected by CCK-8 assay and flow cytometry. The results indicate that U251 human glioma cells were killed by focused ultrasound (FUS) combined with GA/PLGA microbubbles. FUS combined with GA/PLGA microbubbles was capable of locally and transiently enhancing the permeability of BBB under certain conditions. This conformational change allows the release of GA to extracellular space. This study provides novel targets for the treatment of glioma.
研究领域:
药理学
·
肿瘤学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2022
·
IF 5.112
Lili Lin,Saili Xie,Yingzheng Zhao,Zenghui Liang,Qilong Wu,Mingling Fang,Xiaolu Teng,Binbin Shi,Yunjun Yang,Bin Chen
Purpose Acute pancreatitis (AP) involves sudden inflammation caused by abnormal activation of pancreatic enzymes. The mechanisms underlying AP include oxidative stress, high levels of inflammatory mediators and inflammatory cell infiltration. Heparin, a key therapeutic drug, exerts anti-inflammatory, antioxidative, and anticoagulative effects. However, safe and effective drug delivery remains an obstacle. This study is the first to investigate the therapeutic effects of heparin-loaded microbubbles (HPMB) combined with ultrasound (UHPMB) and the role of heparin in acoustic cavitation. Methods The characteristics of the microbubbles, including particle size, concentration, release, stability, and development, were studied. Heparin concentration in the HPMB was measured, and heparin-induced anticoagulation was evaluated. Drug safety was explored using hemolysis and cell viability assessments. The ability of HPMB to alleviate oxidative stress and inflammation were investigated in vitro . L -arginine induces AP in vivo . UHPMB was used for AP treatment. Serum amylase levels were measured and pancreatic architecture and pathological features were evaluated to determine AP severity. In vivo efficacy was evaluated, and the underlying mechanism of heparin action during acoustic cavitation was explored. Results HPMB was spherical and presented as an emulsion-like solution without aggregation. HPMB was visible and stable and effectively released the drug under ultrasound (US). HPMB and UHPMB led to lower AP severity than in the untreated group. US-targeted microbubble destruction (UTMD) enhanced the therapeutic effect by decreasing oxidative stress and inflammation in AP models without injuring vital organs. UHPMB regulated VEGF/Flt-1 and SOD-1 expression. HPMB can also mitigate oxidative stress and inflammation in H 2 O 2 -pretreated cells. Conclusion UHPMB exhibits a strong ability not only to selectively target pancreatic lesions and release heparin but also to provide efficient protection by inhibiting oxidative stress and inflammation.
研究领域:
药理学
·
治疗学
·
医学成像
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED ACOUSTICS
·
2024
·
IF 3.4
Jing Cao,Honghui Xue,Yinuo Zheng,Ling Wang,Litao Sun
Acoustic cavitation serves various therapeutic purposes, with both microbubbles and phase-transit droplets serving as potential cavitation nuclei. This project focused on investigating the intricate interaction between microbubbles and droplets and the resultant impact on acoustic cavitation. To facilitate this investigation, microbubbles with a negative potential of −51.58 mV were prepared, while droplets were endowed with a positive potential of +4.22 mV, facilitating the formation of microbubble-droplet clusters. Microscopic analysis was employed to observe the morphology of these clusters, revealing an initial mean size of 4.85 µm before ultrasound activation and subsequent transformation into larger bubbles with a mean size of 12.54 µm after ultrasound activation. The experimental approach involved the use of varying driven voltages to generate ultrasound waves with different intensities. A passive cavitation detector (PCD) was then employed to capture cavitation signals. Results demonstrated that, when maintaining a microbubble ratio of 50% and varying droplet ratios from 0% to 50%, the driven voltage at which the cavitation peak appeared decreased from 180 mV to 140 mV. Additionally, the mean cavitation intensity exhibited an initial increase from 0.58 to 0.78, followed by a subsequent decrease from 0.78 to 0.63 after normalization. This study provided valuable insights into the dynamic interactions between microbubbles and droplets. Specifically, it showed that microbubble cavitation transferred energy to droplets, leading to the generation of larger bubbles and higher cavitation intensity. Nevertheless, the observed cavitation intensity and threshold were contingent upon the ratios of microbubbles and droplets. Notably, to achieve an ideal cavitation intensity, the energy generated by microbubble cavitation must be substantial enough to activate all droplets, inducing acoustic droplet vaporization (ADV) and cavitation.
研究领域:
医学超声
·
生物医学工程
✓ 已验证
DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 3
·516-524
·
IF 3.929
Wang Jiayu,Li Pan,Tian Rui,Hu Wenjing,Zhang Yuxia,Yuan Pei,Tang Yalan,Jia Yuntao,Zhang Liangke
Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The
prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm ± 421.2 nm and a drug-loading efficiency of 2.23% ± 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release
of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently
enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP-MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation
in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted
drug delivery in clinical therapy and disease diagnosis.
研究领域:
医学影像
·
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2014
·Vol. 11
·期 4
·2413-2420
·
IF 1.484
Jing Ma,Ling Xi Xing,Ming Shen,Fan Li,Ming Jie Zhu,Li Fang Jin,Zhaojun Li,Feng Gao,Yijin Su,You Rong Duan,Lian Fang Du
A combination of diagnostic and therapeutic ultrasound (US) techniques may be able to provide the basis of specific therapeutic protocols, particularly for the treatment of tumors. Nanotechnology may aid the progression towards the use of US for tumor diagnosis and targeted therapy. The current study investigated in vivo and in vitro US contrast imaging using nanocapsules (NCs), and also US and US‑targeted microbubble destruction (UTMD) therapy using drug‑loaded NCs for pancreatic cancer in vitro. In the current study, the NCs were made from the polymer nanomaterial poly(lactic‑co‑glycolic acid)‑monomethoxypoly(ethylene glycol) (PLGA‑mPEG), encapsulated with paclitaxel (PTX), to create PTX‑PLGA‑mPEG NCs. The PTX‑PLGA‑mPEG NCs were used as a US contrast agent (UCA), which produced satisfactory US contrast‑enhanced images in vitro and in vivo of the rabbit kidneys, with good contrast compared with lesions in the peripheral regions. However, clear contrast‑enhanced images were not obtained using PTX‑PLGA‑mPEG NCs as a UCA, when imaging the superficial pancreatic tumors of nude mice in vivo. Subsequently, fluorescence and flow cytometry were used to measure the NC uptake rate of pancreatic tumor cells under various US or UTMD conditions. An MTT assay was used to evaluate the efficiency of PTX and PTX‑PLGA‑mPEG NCs in killing tumor cells following 24 or 48 h of US or UTMD therapy, compared with controls. The specific US or UTMD conditions had been previously demonstrated to be optimal through repeated testing, to determine the conditions by which cells were not impaired and the efficiency of uptake of nanoparticles was highest. The current study demonstrated high cellular uptake rates of PLGA‑mPEG NCs and high tumor cell mortality with PTX‑PLGA‑mPEG NCs under US or UTMD optimal conditions. It was concluded that the use of NCs in US‑mediated imaging and antitumor therapy may provide a novel application for US.
研究领域:
医学影像
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Asia-Pacific Journal of Chemical Engineering
·
2021
·Vol. 17
·期 1
·e2720
·
IF 1.447
Chao Jia,Hu Shen,Yingyu Xu,Xingbang Hu,Guoqiang Yang,Zhibing Zhang
With enormous interfacial area for particle collection, microbubbles exhibit great application prospect in the mineral flotation. Under certain ionic strength, microbubbles can be produced continuously in the microbubble column without extra reagent addition. In this work, multiphase flow characteristics (Sauter mean diameter, bubble size distribution, gas holdup & interfacial area) were studied systematically with variables including the salt type, salt concentration, and operating conditions. Based on mathematical model, critical coalescence concentration was determined for each investigated salt. According to experimental results, a mathematical correlation was established between the Sauter mean diameter and ionic strength. For the formation of microbubble system, the lowest ionic strength was approximately 0.5 mol/L. Multiphase flow characteristics in the microbubble column depended highly on the ionic strength. The interfacial area and gas holdup increased by 38 times and more than 3 times respectively, with the ionic strength of Al 2 (SO 4 ) 3 rising from 0 to 1.5 mol/L. The critical coalescence concentration ranged from 0.037 mol/L (Al 2 (SO 4 ) 3 ) to 0.517 mol/L (NaCl), which correlated with the ionic strength of each salt.
研究领域:
矿物加工工程
·
化学工程
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Lihui Yuwen,Yuan Liu,Fengjiao Xu,Chi Zhang,Xiaolong Chen,Zhaowei Yin,Bin Liang,Lianhui Wang
Bacterial biofilms are difficult to treat with traditional antibiotics. Ultrasound (US)-responsive antibacterial agents have emerged as promising alternatives for the treatment of bacterial biofilm infections. However, they often suffer from antibiotic dependence, lack of targeting, and low antibacterial efficiency. Herein, we develop Fe3O4/MnCO3 microbubbles (FMMB) by self-assembly of Fe3O4 nanoparticles (Fe3O4 NPs) and MnCO3 nanoparticles (MnCO3 NPs). By the direction of magnetic field (MF), FMMB can be targeted to the Staphylococcus aureus (MRSA) biofilm. Under US irradiation, FMMB can destroy the structure of MRSA biofilms by cavitation-induced mechanical effects and kill bacteria by MnCO3 NPs generated reactive oxygen species (ROS) through the sonodynamic effect. In the mice model with catheter MRSA biofilm infection, FMMB removed 70.4% of the biofilm with MF and US, and the bacteria inactivation efficiency reached as high as 99.999% (4.9 Log). This work develops multifunctional microbubbles with both US-responsive mechanical and sonodynamic effects for biofilm destruction and MF-responsive properties for biofilm targeting, which provides a promising strategy for the design of antibiofilm agents to effectively treat bacterial biofilm infections.
研究领域:
医学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICAL PHYSICS
·
2019
·Vol. 46
·期 12
·5467-5477
·
IF 3.177
Diya Wang,Yuchao Sang,Xinyu Zhang,Hong Hu,Shukuan Lu,Yu Zhang,Chaoying Fu,Guy Cloutier,Mingxi Wan
Purpose The Nakagami statistical model and Nakagami shape parameter m have been widely used in linear tissue characterization and preliminarily characterized the envelope distributions of nonlinear encapsulated microbubbles (EMBs). However, the Nakagami distribution of nonlinear scattering EMBs lacked a systematical investigation. Thus, this study aimed to investigate the Nakagami distribution of EMBs and illustrate the impact of EMBs' nonlinearity on the Nakagami model. Method A group of simulated EMB phantoms and in vitro EMB dilutions with an increasing concentration distribution under various EMB nonlinearities, as regulated by acoustic parameters, were characterized by using the window-modulated compounding Greenwood–Durand estimator. Results Raw envelope histograms of simulated and in vitro EMBs were well matched with the Nakagami distribution with a high correlation coefficient of 0.965 ± 0.021 ( P < 0.005). The mean values and gradients of m parameters of simulated and in vitro EMBs were smaller than those of linear scatterers due to the stronger nonlinearity. These m values exhibited a quasi-linear improvement with the increase in second harmonic nonlinear-to-linear component ratio regulated by pulse lengths and excitation frequencies at low- and high-concentration conditions. Conclusions The Nakagami distribution was suitable for the EMBs characterization but the corresponding m parameter was affected by the EMBs' nonlinearity. These validations provided support and nonlinear impact assessment for the EMBs' characterization using the Nakagami statistical model in the future.
研究领域:
超声学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）