A synergistic bactericidal effect of low-frequency and low-intensity ultrasound combined with levofloxacin-loaded PLGA nanoparticles on M. smegmatis in macrophages

Xie, Shuang; Li, Gangjing; Hou, Yuru; Yang, Min; Li, Fahui; Jian-hu, LI; Li, Dairong

doi:10.1186/s12951-020-00658-7

Cited by 24 publications

(19 citation statements)

References 54 publications

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“…In addition to the CTAB turbidimetric method for determining the effective connection of covalent bonds, a change in particle size from the nanometre to the micrometre scale also confirmed the effective connection of HA. 25 Although their particle size increased, the microbubbles remained smaller than red blood cells. HA affected the potential of the microbubbles, which is important for ensuring passage through the capillary network and engulfment by macrophages.…”

Section: Optimal Ha Loading Capacitymentioning

confidence: 99%

Experimental Study on the Compatibility and Characteristics of a Dual-Target Microbubble Loaded with Anti-miR-33

Yuan¹,

Li²,

Liu³

et al. 2021

IJN

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To prepare a new type of dual-target microbubble loaded with anti-miR-33 (ANM33). Methods: Carrier core nanobubbles (NBs) were prepared by thin film hydration, and microbubbles loaded with PM1 (PCNBs) were prepared by grafting DSPE-PEG2000maleimide-PM1 onto the NB surface. ANM33 was connected via electrostatic adsorption and covalent bonding, and hyaluronic acid (HA) was covalently connected. PM1 and HA were the targets, and ANM33 was the intervention drug. To evaluate the general physical and chemical properties of the prepared dual-target microbubbles loaded with ANM33 (HA-PANBs), we observed their morphology, particle size and surface potential while monitoring their stability and in vitro imaging ability, evaluated their toxic effect on cells and verified their ability to target cells. Results: HA-PANBs had a regular morphology and good stability. The average particle size measured by a Malvern potentiometer was 1421.75±163.23 nm, and the average surface potential was −5.51±1.87 mV. PM1 and ANM33 were effectively connected to the NBs. The PM1, ANM33, and HA binding reached 89.0±1.1%, 65.02±5.0%, and 61.4±3.5%, respectively, and the maximum binding reached 2 µg, 5 µg, and 7 µg/10 8 microbubbles, respectively. HA-PANBs had no obvious toxic effects on cells, and their ability to continuously enhance imaging in vitro persisted for more than 15 minutes, obviously targeting foam cells in the early stage of AS. Conclusion: HA-PANBs are ideal ultrasound contrast agents. The successful, firm connection of PM1 and HA to the NBs significantly increased the amount of carried ANM33. When microbubbles prepared with 2:4:7 PM1:ANM33:HA were used as a contrast agent, they had a high ANM33 carrying capacity, stable physical properties, and significantly enhanced imaging and targeting of foam cells in the early stage of AS.

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Section: Optimal Ha Loading Capacitymentioning

confidence: 99%

Experimental Study on the Compatibility and Characteristics of a Dual-Target Microbubble Loaded with Anti-miR-33

Yuan¹,

Li²,

Liu³

et al. 2021

IJN

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“… 44 Xie et al also reported nano-formulated levofloxacin enhanced the killing M. smegmatis in macrophages under ultrasonic treatment. 45 However, these nano-formulated anti-tuberculosis agents delivered the drug to its target using a free passive movement and passive targeting strategy. More research has revealed that active targeting mechanisms are more effective for targeted drug delivery than passive targeting mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…We also speculate that the significant therapeutic effect may be related to the cavitation effect of ultrasound enhancing the permeability of cell membranes to promote drug uptakes. 45 , 50 The results from CLSM and flow cytometry ( Figure 6 ) analysis demonstrated that ultrasound facilitated the increased nanoparticle uptake by macrophage and BCG bacteria, implying that ultrasound can efficiently translocate the drug into the cell where the pathogens reside and replicate. Intracellular drug accumulation then promotes the bacterial uptake of the antimicrobial to achieve the maximum therapeutic benefit of the treatments.…”

Section: Discussionmentioning

confidence: 99%

“…These results are similar to the findings by Xie et al, which showed that ultrasound promoted uptake of nanoparticles by the macrophages, thus enhancing the intracellular bactericidal effect. 45 In addition, IFN-γ is an important mediator of macrophage activation against intracellular pathogens. 51 US+BM2-LVFX-NPs induced more IFN-γ production than other treatment options in this study.…”

Section: Discussionmentioning

confidence: 99%

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Levofloxacin-Loaded Nanosonosensitizer as a Highly Efficient Therapy for Bacillus Calmette-Guérin Infections Based on Bacteria-Specific Labeling and Sonotheranostic Strategy

Jian-hu

Hou

et al. 2021

IJN

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Purpose The rapid emergence of multidrug-resistant Mycobacterium tuberculosis ( MTB ) poses a significant challenge to the treatment of tuberculosis (TB). Sonodynamic antibacterial chemotherapy (SACT) combined with sonosensitizer-loaded nanoparticles with targeted therapeutic function is highly expected to eliminate bacteria without fear of drug resistance. This study aimed to investigate the antibacterial effect and underlying mechanism of levofloxacin-loaded nanosonosensitizer with targeted therapeutic function against Bacillus Calmette-Guérin bacteria ( BCG , an MTB model). Methods This study developed levofloxacin-loaded PLGA-PEG (poly lactide-co-glycolide-polyethylene glycol) nanoparticles with BM2 aptamer conjugation on its surface using the crosslinking agents EDC and NHS (BM2-LVFX-NPs). The average diameter, zeta potential, morphology, drug-loading properties, and drug release efficiency of the BM2-LVFX-NPs were investigated. In addition, the targeting and toxicity of BM2-LVFX-NPs in the subcutaneous BCG infection model were evaluated. The biosafety, reactive oxygen species (ROS) production, cellular phagocytic effect, and antibacterial effect of BM2-LVFX-NPs in the presence of ultrasound stimulations (42 kHz, 0.67 W/cm 2 , 5 min) were also systematically evaluated. Results BM2-LVFX-NPs not only specifically recognized BCG bacteria in vitro but also gathered accurately in the lesion tissues. Drugs loaded in BM2-LVFX-NPs with the ultrasound-responsive feature were effectively released compared to the natural state. In addition, BM2-LVFX-NPs exhibited significant SACT efficiency with higher ROS production levels than others, resulting in the effective elimination of bacteria in vitro. Meanwhile, in vivo experiments, compared with other options, BM2-LVFX-NPs also exhibited an excellent therapeutic effect in a rat model with BCG infection after exposure to ultrasound. Conclusion Our work demonstrated that a nanosonosensitizer formulation with LVFX could efficiently translocate therapeutic drugs into the cell and improve the bactericidal effects under ultrasound, which could be a promising strategy for targeted therapy for MTB infections with high biosafety.

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“…Among them, low-frequency (20 kHz-1 MHz) and lowintensity (20-1000 mW/cm 2 ) ultrasound (LFLIU) is a safe and promising debridement and antibacterial treatment (9,10). The bactericidal effect of LFLIU alone is low, but combined with antibiotics can produce a synergistic bactericidal effect, whether on planktonic bacteria or bacterial biofilms (11)(12)(13). The stable cavitation of LFLIU generated numerous channels on the bacterial membrane and the extracellular matrix of biofilm that promoted the rapid entry of antibiotics into the bacteria, thus significantly increasing the effective concentration of antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Emodin Combined with Multiple Low-frequency Low-intensity Ultrasound to Relieve Osteomyelitis Through Sonoantimicrobial Chemotherapy

et al. 2022

Preprint

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Treatment of osteomyelitis is still challenging as conventional antibiotic therapy is limited by the emergence of resistant strains and the formation of biofilms. Sonoantimicrobial chemotherapy (SACT) is a novel therapy of low-frequency and low-intensity ultrasound (LFLIU) combined with sonosensitizer. Therefore, in our study, a sonosensitizer named emodin (EM) was proposed to be combined with LFLIU to relieve acute osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) through synergistic antibacterial and anti-biofilm effects. The efficiency of different intensities of ultrasound, single (S-LFLIU, 15 min) and multiple ultrasound (M-LFLIU, 5 min every 4 h, three times) against bacteria and biofilm was compared, contributing to develop the best treatment regimen. Our results demonstrated that EM plus S-LFLIU or M-LFLIU (EM+S-LFLIU or EM+M-LFLIU) have significant synergetic bactericidal and anti-biofilm effects and EM+M-LFLIU exhibits superior performance in anti-biofilm. Furthermore, it was suggested that EM+M-LFLIU could produce a large amount of reactive oxygen species (ROS), destroy the integrity of bacterial membrane and wall, down-regulate the expression of oxidative stress, membrane wall synthesis, bacterial virulence and other related genes (agrB, PBP3, sgtB, GMK, zwf, msrA). In vivo study, micro-CT, H&E staining, ELISA assay and bacterial quantification of bone tissue indicated that EM+M-LFLIU could also relieve osteomyelitis of MRSA infection. Our work proffers an original treating bacterial osteomyelitis approach that weakens drug-resistant bacterial and suppresses biofilm formation through SACT, which may provide new prospects for clinical treatment.

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A synergistic bactericidal effect of low-frequency and low-intensity ultrasound combined with levofloxacin-loaded PLGA nanoparticles on M. smegmatis in macrophages

Cited by 24 publications

References 54 publications

Experimental Study on the Compatibility and Characteristics of a Dual-Target Microbubble Loaded with Anti-miR-33

Experimental Study on the Compatibility and Characteristics of a Dual-Target Microbubble Loaded with Anti-miR-33

Levofloxacin-Loaded Nanosonosensitizer as a Highly Efficient Therapy for Bacillus Calmette-Guérin Infections Based on Bacteria-Specific Labeling and Sonotheranostic Strategy

Emodin Combined with Multiple Low-frequency Low-intensity Ultrasound to Relieve Osteomyelitis Through Sonoantimicrobial Chemotherapy

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