Ultrasonic Therapy

超声治疗
  • 文章类型: Journal Article
    背景:放射治疗(RT)是一种广泛使用的肿瘤治疗方法,而这种治疗方式的主要障碍是肿瘤细胞表现出的放射抗性。为了提高RT的有效性,科学家们已经探索了放射增敏方法,包括使用放射增敏剂和物理刺激。然而,几种方法表现出令人失望的结果,包括不良反应和疗效有限.一种更安全,更有效的放射增敏方法涉及低强度超声(LIUS),选择性靶向肿瘤组织并增强放射治疗的疗效。
    方法:本文总结了肿瘤放射抗性的原因,并探讨了LIUS潜在的放射增敏机制。此外,它涵盖了LIUS在放射增敏方面的不同应用策略,包括单独使用LIUS,超声靶向血管内微气泡破坏,超声介导的靶向放射增敏剂递送,和声动力疗法。最后,该综述介绍了在临床环境中采用LIUS-RT联合治疗的局限性和前景,强调需要将研究成果与实际应用联系起来。
    结论:LIUS采用具有成本效益的设备来促进肿瘤放射增敏,减少辐射暴露,提高患者的生活质量。这种功效归因于LIUS利用热量的能力,空化,和机械效应来克服肿瘤细胞对RT的抗性。多项实验分析强调了LIUS使用多种策略诱导肿瘤放射增敏的有效性。虽然初步研究显示出了有希望的结果,进行更全面的临床试验对于确认其在现实世界中的安全性和有效性至关重要。
    BACKGROUND: Radiotherapy (RT) is a widely utilized tumor treatment approach, while a significant obstacle in this treatment modality is the radioresistance exhibited by tumor cells. To enhance the effectiveness of RT, scientists have explored radiosensitization approaches, including the use of radiosensitizers and physical stimuli. Nevertheless, several approaches have exhibited disappointing results including adverse effects and limited efficacy. A safer and more effective method of radiosensitization involves low-intensity ultrasound (LIUS), which selectively targets tumor tissue and enhances the efficacy of radiation therapy.
    METHODS: This review summarized the tumor radioresistance reasons and explored LIUS potential radiosensitization mechanisms. Moreover, it covered diverse LIUS application strategies in radiosensitization, including the use of LIUS alone, ultrasound-targeted intravascular microbubble destruction, ultrasound-mediated targeted radiosensitizers delivery, and sonodynamic therapy. Lastly, the review presented the limitations and prospects of employing LIUS-RT combined therapy in clinical settings, emphasizing the need to connect research findings with practical applications.
    CONCLUSIONS: LIUS employs cost-effective equipment to foster tumor radiosensitization, curtail radiation exposure, and elevate the quality of life for patients. This efficacy is attributed to LIUS\'s ability to utilize thermal, cavitation, and mechanical effects to overcome tumor cell resistance to RT. Multiple experimental analyses have underscored the effectiveness of LIUS in inducing tumor radiosensitization using diverse strategies. While initial studies have shown promising results, conducting more comprehensive clinical trials is crucial to confirm its safety and effectiveness in real-world situations.
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  • 文章类型: Journal Article
    检测并分析IIIB期前列腺炎患者低强度脉冲超声(LIPUS)治疗前后前列腺分泌物(EPS)中微生物的变化。探讨LIPUS治疗慢性前列腺炎(CP)的作用机制。在LIPUS治疗之前和之后,将25例IIIB前列腺炎患者(使用Dirichlet-多项方法估计研究能力,使用25个样本量在α=0.05时达到96.5%)分为两组。采用高通量第二代测序技术检测并分析处理前后EPS中细菌16s核糖体可变区的相对丰度。通过生物信息学软件和数据库对数据进行分析,与P<0.05的差异被认为具有统计学意义。Beta多样性剖析显示,各组间存在显著差别(P=0.046)。LEfSe在LIPUS治疗前后检测到IIIB前列腺炎患者EPS中的四种特征微生物。通过DESeq2方法在组间进行多重比较后,发现了六种不同的微生物。LIPUS可以通过改变EPS的菌群结构改善患者的临床症状,稳定和影响常驻细菌或机会性病原体。
    To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients\' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens.
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  • 文章类型: Journal Article
    探讨聚焦超声联合等离子射频消融技术对持续性应变性鼻炎生理稳定性及术后恢复的影响。对于对照实验,选择90例持续性应变性鼻炎患者,分为对照组(CG)和实验组(EG)。CG使用传统的射频消融技术,而EG采用聚焦超声技术结合射频消融技术治疗持续性应变性鼻炎。在EG和CG之间,比较和对比鼻腔症状的恢复,鼻部体征,术后不适,术后呼吸状态。手术后四分之一,EG和CG之间的体征评分有很大差异,治疗6个月后观察到特别显著的差异。手术一年后,在不同间隔的有效率比较中,EG和CG之间存在统计学差异,P值为.013。手术后6个月,EG和CG比较鼻功能的MTT时间分别为12.632.65和17.682.84,具有统计学上的显著差异。在MTR比较中EG和CG之间的差异具有统计学意义。比较不同处理时间后EG和CG之间的NNO值。EG患者的一氧化氮值随着时间的推移而下降,术后1个月和术后1年有统计学意义。从各种症状有效率的比较中可以明显看出,EG比CG具有更高的治疗有效率,术后总治疗效果差异有统计学意义。PONV的指标,PA,定向能力,呼吸恢复,嗅觉恢复在EG中比在CG中表现更好,差异有统计学意义。聚焦超声和等离子射频消融技术在治疗持续性应变性鼻炎中具有良好的治疗效果,并能显著降低MTT。这项技术可以有效改善鼻塞等症状,鼻流,患者头痛,治疗效果持久。治疗后住院时间明显缩短。
    Examine the effects of focused ultrasound in combination with plasma radiofrequency ablation technology on the physiological stability and postoperative recovery of persistent strain rhinitis. For a control experiment, 90 patients with persistent strain rhinitis were chosen and split into two groups: the control group (CG) and the experimental group (EG). The CG used conventional radiofrequency ablation technology, while the EG used focused ultrasound technology combined with radiofrequency ablation technology to treat persistent strain rhinitis. Between the EG and the CG, compare and contrast the recovery of nasal symptoms, nasal signs, postoperative discomfort, and postoperative respiratory status. One quarter after surgery, there was a substantial difference in physical sign ratings between the EG and the CG, and a particularly significant difference was seen after six months of treatment. One year following surgery, there was a statistical difference between the EG and the CG in the comparison of effective rates at various intervals, with a P value of .013. At 6 months following surgery, the MTT times in the EG and CG for the comparison of nasal function were 12.63 2.65 and 17.68 2.84, respectively, with statistically significant differences. The difference between the EG and the CG in the MTR comparison is statistically significant. In the comparison of NNO values between the EG and the CG after different treatment times. The nitric oxide value of the EG patients decreased over time, with statistical significance one month after surgery and one year after surgery. It is evident from the comparison of various symptom efficacy rates that the EG has a higher treatment effectiveness rate than the CG, and the total treatment effect difference following surgery has statistical significance. Indicators for PONV, PA, directional ability, respiratory recovery, and olfactory recovery performed better in the EG than in the CG, and the differences were statistically significant. Focused ultrasound and plasma radiofrequency ablation technology have a good therapeutic impact in the treatment of persistent strain rhinitis and can significantly reduce MTT. This technology can effectively improve symptoms such as nasal congestion, nasal flow, and headache in patients, and the therapeutic effect is long-lasting. The hospitalization time after treatment is significantly shortened.
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  • 文章类型: Journal Article
    背景:乳腺癌是全球最常见的恶性肿瘤,肺癌后。在乳腺癌的各种亚型中,HER2阳性乳腺癌(HER2BC)由于其增加的侵袭性和转移潜力而提出了特别具有挑战性的预后。本研究的目的是构建基于聚(偏二氟乙烯-三氟乙烯)(P(VDF-TrFE))的复合压电纳米粒子,用于HER2BC的成像和治疗。
    方法:通过重塑P(VDF-TrFE)压电纳米颗粒的晶体结构,改善亲水性,并结合成像功能,我们开发了集成成像和治疗功能的压电复合纳米粒子(PGd@tNBs)。体外表征包括对压电性能的评估,亲水性,成像性能,和这些颗粒的治疗效果。PGd@tNBs颗粒的靶向和治疗有效性在SK-BR3细胞系中进一步验证,随后在HER2阳性荷瘤小鼠中证实。
    结果:纳米颗粒表现出优异的生物相容性和令人印象深刻的多模态成像性能。磁共振成像(MRI)观察显示PGd@tNBs颗粒在HER2阳性肿瘤中显著积累,与传统超声造影剂相比,具有优越的超声造影性能,和小动物体内成像显示PGd@tNBs颗粒主要通过呼吸和尿液代谢排出。压电显微镜表征强调了PGd@tNBs颗粒的出色压电性能。在靶向结合HER2-BC后,超声刺激影响细胞膜电位,导致可逆电穿孔。这个,反过来,影响细胞内外钙离子的平衡和线粒体膜电位。在被细胞摄取后,PGd@tNB,当暴露于超声波时,触发了活性氧(ROS)的产生,导致谷胱甘肽和超氧化物歧化酶的消耗,并实现声动力治疗。值得注意的是,重复超声刺激,PGd@tNBs颗粒结合并进入细胞后,增加ROS的产生并将凋亡率提高约45%。
    结论:结论:开发的PGd@tNBs颗粒表现出出色的成像和治疗效果,具有精确诊断和个性化治疗HER2BC的潜力。
    BACKGROUND: Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2 BC)poses a particularly challenging prognosis due to its heightened invasiveness and metastatic potential. The objective of this study was to construct a composite piezoelectric nanoparticle based on poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for imaging and treatment of HER2 BC.
    METHODS: By reshaping the crystal structure of P(VDF-TrFE) piezoelectric nanoparticles, improving hydrophilicity, and incorporating imaging capabilities, we developed piezoelectric composite nanoparticles (PGd@tNBs) that integrate imaging and therapeutic functions. The in vitro characterization encompassed the assessment of piezoelectric properties, hydrophilicity, imaging performance, and therapeutic efficacy of these particles. The targeting and therapeutic effectiveness of PGd@tNBs particles were further validated in the SK-BR3 cell line and subsequently confirmed in HER2-positive tumor-bearing mice.
    RESULTS: The nanoparticle demonstrated excellent biocompatibility and impressive multimodal imaging performance. Magnetic resonance imaging (MRI) observations revealed significant accumulation of PGd@tNBs particles in the HER2 positive tumor, exhibiting superior contrast-enhanced ultrasound performance compared to traditional ultrasound contrast agents, and small animal in vivo imaging showed that PGd@tNBs particles were primarily excreted through respiration and urinary metabolism. Piezoforce Microscopy characterization highlighted the outstanding piezoelectric properties of PGd@tNBs particles. Upon targeted binding to HER2-BC, ultrasound stimulation influenced the cell membrane potential, leading to reversible electroporation. This, in turn, affected the balance of calcium ions inside and outside the cells and the mitochondrial membrane potential. Following ingestion by cells, PGd@tNBs, when exposed to ultrasound, triggered the generation of reactive oxygen species (ROS), resulting in the consumption of glutathione and superoxide dismutase and achieving sonodynamic therapy. Notably, repeated ultrasound stimulation, post PGd@tNBs particles binding and entry into cells, increased ROS production and elevated the apoptosis rate by approximately 45%.
    CONCLUSIONS: In conclusion, the PGd@tNBs particles developed exhibit outstanding imaging and therapeutic efficacy, holding potential for precise diagnosis and personalized treatment of HER2 BC.
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  • 文章类型: Journal Article
    伤口感染,特别是那些由致病菌引起的,由于相关的并发症和不良的治疗结果,引起了相当大的公共卫生问题。在这里,我们开发了抗菌纳米粒子,即,PGTP,通过将胍衍生物与基于卟啉的声敏剂配位。合成的PGTP纳米粒子,以它们的强正电荷为特征,通过电荷干扰有效地破坏细菌的生物合成过程,证明对革兰氏阴性和革兰氏阳性细菌的功效。此外,PGTP纳米粒子在超声刺激下产生活性氧,导致生物膜完整性的破坏和病原体的有效消除。RNA-seq分析揭示了伤口愈合的详细机制,揭示了PGTP纳米粒子,当加上超声波时,通过干扰氨基酸的合成和转录来损害细菌代谢。这项研究提出了一种通过超声驱动的电荷干扰治疗来对抗伤口感染的新方法,由先进的抗菌纳米材料促进。
    Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.
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  • 文章类型: Journal Article
    声动力疗法(SDT)与角化术的结合用于靶向癌症治疗是肿瘤学的重大进展。在这里,我们提出了一个双重反应的治疗系统,\"CytoNano\",它结合了注入有氮化铜纳米颗粒和富氧全氟化碳(Lip@Cu3N/PFC-O2)的阳离子脂质体,全部包裹在嗜中性粒细胞膜和酸响应性羧甲基纤维素的仿生涂层中。CytoNano利用中性粒细胞和酸响应材料的细胞模拟,能够精确靶向肿瘤及其酸性微环境。这种战略设计促进了Lip@Cu3N/PFC-O2在肿瘤内的靶向释放,增强癌细胞摄取和线粒体定位。因此,它放大了Cu3N驱动的SDT和角化术的治疗功效,同时保留了健康组织。此外,CytoNano的超声反应性增强肿瘤内氧合,克服生理障碍并启动诱导多个细胞死亡途径的组合的声动力-铜质子效应。因此,我们开创了一种精确的声动力学角化的仿生方法,彻底改变癌症疗法。
    The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, \"CytoNano\", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu3N/PFC-O2), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu3N/PFC-O2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu3N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano\'s ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.
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  • 文章类型: Journal Article
    本研究旨在探讨可行性,功效,聚焦超声(FUS)治疗伴有持续症状的外阴低度鳞状上皮内病变(VLSIL)的安全性。
    这项回顾性分析包括24例接受FUS治疗的VLSIL患者。在每次后续访问中,评估了临床反应,包括症状和体征的变化.此外,根据第3次随访的外阴活检结果评估组织学反应.评估临床和组织学反应以阐明功效。
    共有22名患者完成了随访和治疗后的病理活检。治疗后,瘙痒的临床评分从2.55±0.51降至0.77±0.81(p<0.05)。此外,临床有效率和组织学有效率分别为86.4%和81.8%,分别。只有2例治愈的患者在随访期间第3年和第4年复发,并在再次治疗后治愈。在不利影响方面,只有一名患者在治疗后出现溃疡,对症抗炎治疗后愈合,没有疤痕,在任何患者中均未发现其他治疗并发症。在随访期间,没有患者发生恶性转化。
    这项研究表明FUS是可行的,有效,并且可以安全地治疗具有持续症状的VLSIL患者,为有症状的VLSIL的无创治疗提供了新的解决方案。
    UNASSIGNED: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms.
    UNASSIGNED: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy.
    UNASSIGNED: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period.
    UNASSIGNED: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.
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  • 文章类型: Journal Article
    乳腺癌骨转移是一种晚期疾病,通常采用放疗和化疗治疗,这导致严重的副作用和有限的有效性。为了改善这一点,声动力疗法可能是未来更安全有效的方法。细菌外膜囊泡(OMV)具有优异的免疫调节特性,包括调节巨噬细胞极化,促进DC细胞成熟,增强抗肿瘤作用。将OMV与声动力疗法结合可以产生协同抗肿瘤作用。因此,我们构建了多功能纳米颗粒用于治疗乳腺癌骨转移。我们将乳腺癌细胞膜和细菌外膜囊泡融合形成杂化膜(HM),然后将负载IR780的PLGA与HM封装在一起以产生纳米颗粒,IR780@PLGA@HM,具有肿瘤靶向性,免疫调节,和声动力学能力。实验表明,IR780@PLGA@HM纳米粒子具有良好的生物相容性,有效靶向4T1肿瘤,促进巨噬细胞I型极化和DC细胞活化,抗肿瘤炎症因子表达增强,并表现出在体外和体内有效杀死肿瘤的能力,对乳腺癌骨转移有很好的治疗效果。因此,我们构建的纳米颗粒为有效治疗乳腺癌骨转移提供了新的策略。
    Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.
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  • 文章类型: Journal Article
    化学治疗剂在对抗肿瘤方面具有显著的临床潜力。然而,将这些药物递送到肿瘤部位进行控制释放仍然是一个关键的挑战。在这项研究中,我们合成并构建了谷胱甘肽(GSH)和酸双响应铋基纳米递送平台(BOD),旨在增强多西他赛(DTX)介导的肿瘤治疗的声动力学。铋纳米材料在超声刺激下可产生多种活性氧(ROS)。此外,负载DTX形成BOD有效降低DTX在血液中的毒性,确保其细胞毒性作用主要在肿瘤部位发挥。DTX可以在高表达的GSH和酸性肿瘤微环境中很好地释放。同时,超声还可以促进DTX的释放。体外和体内实验的结果均证实,涉及化学疗法和声动力疗法(SDT)的协同疗法可显着抑制肿瘤细胞的生长和增殖。本研究为开发肿瘤微环境反应和超声促进药物释放的协同肿瘤治疗平台提供了有利的范例。
    Chemotherapeutic agents hold significant clinical potential in combating tumors. However, delivering these drugs to the tumor site for controlled release remains a crucial challenge. In this study, we synthesize and construct a glutathione (GSH) and acid dual-responsive bismuth-based nano-delivery platform (BOD), aiming for sonodynamic enhancement of docetaxel (DTX)-mediated tumor therapy. The bismuth nanomaterial can generate multiple reactive oxygen species under ultrasound stimulation. Furthermore, the loading of DTX to form BOD effectively reduces the toxicity of DTX in the bloodstream, ensuring its cytotoxic effect is predominantly exerted at the tumor site. DTX can be well released in high expression of GSH and acidic tumor microenvironment. Meanwhile, ultrasound can also promote the release of DTX. Results from bothin vitroandin vivoexperiments substantiate that the synergistic therapy involving chemotherapy and sonodynamic therapy significantly inhibits the growth and proliferation of tumor cells. This study provides a favorable paradigm for developing a synergistic tumor treatment platform for tumor microenvironment response and ultrasound-promoted drug release.
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  • 文章类型: Journal Article
    植入物感染是临床治疗中的严重并发症,通常伴随着具有高抗生素抗性的细菌生物膜的形成。声动力疗法(SDT)是一种无抗生素的方法,可以在超声(US)治疗下产生活性氧(ROS)以杀死细菌。然而,细菌生物膜的胞外聚合物(EPS)屏障和低氧微环境显着限制了SDT的抗生物膜活性。在这项研究中,开发了负载有镓原卟啉IX(GaPPIX)和氧气(O2)(LPGOND)的脂壳全氟戊烷(PFP)纳米液滴,用于治疗植入物感染。在美国的刺激下,LPGOND由于液-气相变而经历空化效应并像炸弹一样破坏生物膜结构。同时,美国刺激后,LPGONDs释放O2和GaPPIX。释放的O2可以缓解生物膜中的低氧微环境,并通过GaPPIX增强ROS的形成,以增强细菌杀伤。体内实验结果表明,LPGONDs可以通过破坏生物膜结构有效治疗小鼠模型中耐甲氧西林金黄色葡萄球菌(MRSA)的植入物感染,缓解缺氧,并通过SDT增强细菌杀灭能力。因此,这项工作提供了一种新的多功能超声增敏剂,以克服SDT治疗植入物感染的局限性。
    Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.
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