RESUMEN
Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (â¢OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.
Asunto(s)
Clorofilidas , Indoles , Platino (Metal) , Polímeros , Porfirinas , Neoplasias de la Tiroides , Microambiente Tumoral , Terapia por Ultrasonido , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/metabolismo , Humanos , Línea Celular Tumoral , Microambiente Tumoral/efectos de los fármacos , Indoles/química , Terapia por Ultrasonido/métodos , Porfirinas/química , Porfirinas/farmacología , Polímeros/química , Animales , Platino (Metal)/química , Platino (Metal)/uso terapéutico , Platino (Metal)/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Apoptosis/efectos de los fármacos , Nanopartículas/química , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Quinolinas/farmacología , Quinolinas/química , Ratones Desnudos , Portadores de Fármacos/químicaRESUMEN
Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.
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Terapia por Ultrasonido , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Terapia por Ultrasonido/métodos , Ratas Sprague-Dawley , Ratas , Staphylococcus aureus/efectos de los fármacos , Óxido de Zinc/química , Ratones , Estimulación Eléctrica , Masculino , Infecciones Estafilocócicas/terapia , Poliésteres/química , Especies Reactivas de Oxígeno/metabolismo , Terapia por Estimulación Eléctrica/métodos , Neovascularización Fisiológica/efectos de los fármacosRESUMEN
Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-â ¡ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate â¼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-â ¡ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).
Asunto(s)
Bismuto , Neoplasias de la Mama , Oxígeno , Terapia por Ultrasonido , Bismuto/química , Femenino , Animales , Neoplasias de la Mama/terapia , Terapia por Ultrasonido/métodos , Oxígeno/química , Ratones , Ratones Endogámicos BALB C , Humanos , Línea Celular Tumoral , Rayos Infrarrojos , Nanoestructuras/química , Fototerapia/métodosRESUMEN
Ferroptosis, a recently identified form of cell death, holds promise for cancer therapy, but concerns persist regarding its uncontrolled actions and potential side effects. Here, we present a semiconducting polymer nanoprodrug (SPNpro) featuring an innovative ferroptosis prodrug (DHU-CBA7) to induce sono-activatable ferroptosis for tumor-specific therapy. DHU-CBA7 prodrug incorporate methylene blue, ferrocene and urea bond, which can selectively and specifically respond to singlet oxygen (1O2) to turn on ferroptosis action via rapidly cleaving the urea bonds. DHU-CBA7 prodrug and a semiconducting polymer are self-assembled with an amphiphilic polymer to construct SPNpro. Ultrasound irradiation of SPNpro leads to the production of 1O2 via sonodynamic therapy (SDT) of the semiconducting polymer, and the generated 1O2 activated DHU-CBA7 prodrug to achieve sono-activatable ferroptosis. Consequently, SPNpro combine SDT with the controlled ferroptosis to effectively cure 4T1 tumors covered by 2-cm tissue with a tumor inhibition efficacy as high as 100 %, and also completely restrain tumor metastases. This study introduces a novel sono-activatable prodrug strategy for regulating ferroptosis, allowing for precise cancer therapy.
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Ferroptosis , Ratones Endogámicos BALB C , Polímeros , Profármacos , Semiconductores , Ferroptosis/efectos de los fármacos , Profármacos/farmacología , Profármacos/química , Profármacos/uso terapéutico , Animales , Polímeros/química , Femenino , Línea Celular Tumoral , Ratones , Terapia por Ultrasonido/métodos , Nanopartículas/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Oxígeno Singlete/metabolismoRESUMEN
Introduction: Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death. Methods: Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed. Results: SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo. Conclusion: SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.
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Clorofilidas , Peroxidación de Lípido , Liposomas , Porfirinas , Especies Reactivas de Oxígeno , Sorafenib , Terapia por Ultrasonido , Animales , Liposomas/química , Peroxidación de Lípido/efectos de los fármacos , Sorafenib/farmacología , Sorafenib/química , Terapia por Ultrasonido/métodos , Ratones , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Porfirinas/química , Porfirinas/farmacología , Porfirinas/administración & dosificación , Femenino , Ratones Endogámicos BALB C , Nanopartículas/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Glutatión/metabolismo , Muerte Celular/efectos de los fármacosRESUMEN
Pathogen-host competition for manganese and intricate immunostimulatory pathways severely attenuates the efficacy of antibacterial immunotherapy against biofilm infections associated with orthopaedic implants. Herein, we introduce a spatiotemporal sono-metalloimmunotherapy (SMIT) strategy aimed at efficient biofilm ablation by custom design of ingenious biomimetic metal-organic framework (PCN-224)-coated MnO2-hydrangea nanoparticles (MnPM) as a metalloantibiotic. Upon reaching the acidic H2O2-enriched biofilm microenvironment, MnPM can convert abundant H2O2 into oxygen, which is conducive to significantly enhancing the efficacy of ultrasound (US)-triggered sonodynamic therapy (SDT), thereby exposing bacteria-associated antigens (BAAs). Moreover, MnPM disrupts bacterial homeostasis, further killing more bacteria. Then, the Mn ions released from the degraded MnO2 can recharge immune cells to enhance the cGAS-STING signaling pathway sensing of BAAs, further boosting the immune response and suppressing biofilm growth via biofilm-specific T cell responses. Following US withdrawal, the sustained oxygenation promotes the survival and migration of fibroblasts, stimulates the expression of angiogenic growth factors and angiogenesis, and neutralizes excessive inflammation. Our findings highlight that MnPM may act as an immune costimulatory metalloantibiotic to regulate the cGAS-STING signaling pathway, presenting a promising alternative to antibiotics for orthopaedic biofilm infection treatment and pro-tissue repair.
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Biopelículas , Compuestos de Manganeso , Óxidos , Oxígeno , Biopelículas/efectos de los fármacos , Animales , Ratones , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Oxígeno/metabolismo , Óxidos/farmacología , Óxidos/química , Antibacterianos/farmacología , Peróxido de Hidrógeno/metabolismo , Inmunoterapia/métodos , Humanos , Terapia por Ultrasonido/métodos , Nanopartículas/química , Transducción de Señal/efectos de los fármacos , Antígenos Bacterianos/inmunología , Staphylococcus aureus/efectos de los fármacos , FemeninoRESUMEN
OBJECTIVE: Sonodynamic therapy (SDT) is gaining attention as a promising new noninvasive brain tumor treatment that targets and selectively kills tumor cells, with limited side effects. This review examines the mechanisms of SDT and ongoing clinical trials looking at optimization of sonication parameters for potential treatment of glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). The results in the first patient with recurrent GBM treated at the Mayo Clinic are briefly discussed. METHODS: The authors of this literature review used electronic databases including PubMed, EMBASE, and OVID. Articles reporting relevant preclinical and clinical trials were identified by searching for text words/phrases and MeSH terms, including the following: "sonodynamic therapy," "SDT," "focused ultrasound," "5-ALA," "ALA," "brain tumors," "diffuse pontine glioma," "glioblastoma," and "high grade glioma." RESULTS: Preclinical and clinical trials investigating the specific use of SDT in brain tumors were reviewed. In preclinical models of high-grade glioma and GBM, SDT has shown evidence of targeted tumor cell death via the production of reactive oxygen species. Emerging clinical trial results within recurrent GBM and DIPG show evidence of successful treatment response, with minimal side effects experienced by recruited patients. So far, SDT has been shown to be a promising noninvasive cancer treatment that is well tolerated by patients. The authors present pilot data suggesting good radiological response of GBM to a single SDT treatment, with unpublished observation of a lack of off-target effects even after multiple (monthly) sonication outpatient treatments. The scope of the clinical trials of SDT is to investigate whether it can be the means by which the fatal diagnosis of GBM or DIPG is converted into that of a chronic, treatable disease. CONCLUSIONS: SDT is safe, repeatable, and better tolerated than both chemotherapy and radiotherapy. It has been shown to have an effect in human cancer therapy, but more clinical trials are needed to establish standardized protocols for sonosensitizer delivery, treatment parameters, and combination therapies. The most appropriate timing of treatment also remains to be determined-whether to prevent recurrence in the postoperative period, or as a salvage option in patients with recurrent GBM for which redo surgery is inappropriate. It is hoped that SDT will also be developed for a wider spectrum of clinical indications, such as metastases, meningioma, and low-grade glioma. Further clinical trials are in preparation.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/terapia , Terapia por Ultrasonido/métodos , Glioblastoma/terapia , Neoplasias del Tronco Encefálico/terapia , Glioma Pontino Intrínseco Difuso/terapiaRESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood-brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders. OBJECTIVES: We aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model. METHODS: The ALS mouse model with the SOD1G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining. RESULTS: Compared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord. CONCLUSION: These preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.
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Esclerosis Amiotrófica Lateral , Modelos Animales de Enfermedad , Ratones Transgénicos , Corteza Motora , Animales , Ratones , Corteza Motora/efectos de los fármacos , Corteza Motora/fisiopatología , Glucósidos/farmacología , Glucósidos/administración & dosificación , Microburbujas , Sistemas de Liberación de Medicamentos , Terapia por Ultrasonido/métodos , Superóxido Dismutasa-1/genética , Furanos/farmacología , Furanos/administración & dosificación , Masculino , MutaciónRESUMEN
OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.
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Ratas Sprague-Dawley , Lesiones Intraepiteliales Escamosas , Animales , Femenino , Ratas , Lesiones Intraepiteliales Escamosas/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/terapia , Terapia por Ultrasonido/métodos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Sonothrombolysis is a technique that employs the ultrasound waves to break down the clot. Recent studies have demonstrated significant improvement in the treatment efficacy when combining two ultrasound waves of different frequencies. Nevertheless, the findings remain conflicted on the ideal frequency pairing that leads to an optimal treatment outcome. Existing experimental studies are constrained by the limited range of frequencies that can be investigated, while numerical studies are typically confined to spherical microbubble dynamics, thereby restricting the scope of the analysis. To overcome this, the present study investigated the microbubble dynamics caused by the different combinations of ultrasound frequencies. This was carried out using computational modelling as it enables the visualisation of the microbubble behaviour, which is difficult in experimental studies due to the opacity of blood. The results showed that the pairings of two ultrasound waves with low frequencies generally produced stronger cavitation and higher flow-induced shear stress on the clot surface. However, one should avoid the frequency pairings that are integer multipliers of each other, i.e., frequency ratio of 1/3, 1/2 and 2, as they led to resultant wave with low pressure amplitude that weakened the cavitation. At 0.5 + 0.85 MHz, the microbubble caused the highest shear stress of 60.5 kPa, due to its large translational distance towards the clot. Although the pressure threshold for inertial cavitation was reduced using dual-frequency ultrasound, the impact of the high-speed jet can only be realised when the microbubble travelled close to the clot. The results obtained from the present study provide groundwork for deeper understanding on the microbubble dynamics during dual-frequency sonothrombolysis, which is of paramount importance for its optimisations and the subsequent clinical translation.
Asunto(s)
Simulación por Computador , Microburbujas , Terapia por Ultrasonido , Humanos , Terapia por Ultrasonido/métodos , Modelos Cardiovasculares , Trombosis/diagnóstico por imagenRESUMEN
The current study explores the potential of ultrasound-assisted laser therapy (USaLT) to selectively destroy melanoma cells. The technology was tested on an ex vivo melanoma model, which was established by growing melanoma cells in chicken breast tissue. Ultrasound-only and laser-only treatments were used as control groups. USaLT was able to effectively destroy melanoma cells and selectively remove 66.41% of melanoma cells in the ex vivo tumor model when an ultrasound peak negative pressure of 2 MPa was concurrently applied with a laser fluence of 28 mJ/cm2 at 532 nm optical wavelength for 5 min. The therapeutic efficiency was further improved with the use of a higher laser fluence, and the treatment depth was improved to 3.5 mm with the use of 1,064 nm laser light at a fluence of 150 mJ/cm2. None of the laser-only and ultrasound-only treatments were able to remove any melanoma cells. The treatment outcome was validated with histological analyses and photoacoustic imaging. This study opens the possibility of USaLT for melanoma that is currently treated by laser therapy, but at a much lower laser fluence level, hence improving the safety potential of laser therapy.
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Pollos , Melanoma , Animales , Melanoma/radioterapia , Melanoma/patología , Terapia por Ultrasonido/métodos , Terapia por Láser/métodos , Línea Celular Tumoral , Técnicas Fotoacústicas/métodosAsunto(s)
Técnicas Cosméticas , Rejuvenecimiento , Envejecimiento de la Piel , Terapia por Ultrasonido , Humanos , Envejecimiento de la Piel/efectos de la radiación , Terapia por Ultrasonido/métodos , Terapia por Ultrasonido/efectos adversos , Técnicas Cosméticas/efectos adversos , Resultado del Tratamiento , Piel/efectos de la radiaciónRESUMEN
The exponential growth of therapeutic ultrasound applications demonstrates the power of the technology to leverage the combinations of transducer technology and treatment monitoring techniques to effectively control the preferred bioeffect to elicit the desired clinical effect.Objective: This review provides an overview of the most commonly used bioeffects in therapeutic ultrasound and describes existing transducer technologies and monitoring techniques to ensure treatment safety and efficacy.Methods and materials: Literature reviews were conducted to identify key choices that essential in terms of transducer design, treatment parameters and procedure monitoring for therapeutic ultrasound applications. Effective combinations of these options are illustrated through descriptions of several clinical indications, including uterine fibroids, prostate disease, liver cancer, and brain cancer, that have been successful in leveraging therapeutic ultrasound to provide effective patient treatments.Results: Despite technological constraints, there are multiple ways to achieve a desired bioeffect with therapeutic ultrasound in a target tissue. Visualizations of the interplay of monitoring modality, bioeffect, and applied acoustic parameters are presented that demonstrate the interconnectedness of the field of therapeutic ultrasound. While the clinical indications explored in this review are at different points in the clinical evaluation path, based on the ever expanding research being conducted in preclinical realms, it is clear that additional clinical applications of therapeutic ultrasound that utilize a myriad of bioeffects will continue to grow and improve in the coming years.Conclusions: Therapeutic ultrasound will continue to improve in the next decades as the combination of transducer technology and treatment monitoring techniques will continue to evolve and be translated in clinical settings, leading to more personalized and efficient therapeutic ultrasound mediated therapies.
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Transductores , Terapia por Ultrasonido , Humanos , Terapia por Ultrasonido/métodosRESUMEN
Engineering Z-scheme heterojunctions represents a promising strategy for optimizing the separation and migration of charge carriers in semiconductor sonosensitizers for enhanced reactive oxygen species (ROS) generation. Nevertheless, establishing a continuous and directional pathway for ultrasonic-induced charge flow in Z-scheme heterojunctions remains a significant challenge. In this study, we present a ternary Bi2WO6/TiO2-Pt heterojunction sonosensitizer achieved through the precise growth of Pt nanocrystals on a directionally assembled Bi2WO6/TiO2 Z-scheme structure. The construction of the Bi2WO6/TiO2-Pt heterojunction involves directional growth of Bi2WO6 in situ on the highly exposed (001) crystal facet of TiO2 nanosheets, followed by the precise deposition of nano Pt on the edge (101) crystal facet. The Z-scheme Bi2WO6/TiO2 in the ternary heterojunction ensures effective electron separation, while the Schottky TiO2-Pt interface establishes a well-defined charge flow path and robust redox capabilities. Moreover, nano Pt confers the Bi2WO6/TiO2-Pt heterojunction with excellent peroxidase-mimic and catalase-mimic activities, facilitating interactions with endogenous H2O2 to produce the hydroxyl radicals and O2. It effectively alleviates tumor hypoxia and enhances ROS production. This results in significantly higher efficiency in sonodynamically induced ROS generation compared to pure TiO2 or binary Bi2WO6/TiO2 heterojunctions, as confirmed by DFT theoretical calculation and experiments with both in vitro and in vivo anticancer performance. This study offers valuable insights for designing high-performance Z-scheme sonosensitizer systems.
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Platino (Metal) , Titanio , Titanio/química , Titanio/farmacología , Animales , Platino (Metal)/química , Platino (Metal)/farmacología , Humanos , Ratones , Bismuto/química , Bismuto/farmacología , Especies Reactivas de Oxígeno/metabolismo , Terapia por Ultrasonido , Antineoplásicos/farmacología , Antineoplásicos/química , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacosRESUMEN
BACKGROUND: The insula and dorsal anterior cingulate cortex (dACC) are core brain regions involved in pain processing and central sensitization, a shared mechanism across various chronic pain conditions. Methods to modulate these regions may serve to reduce central sensitization, though it is unclear which target may be most efficacious for different measures of central sensitization. OBJECTIVE/HYPOTHESIS: Investigate the effect of low-intensity focused ultrasound (LIFU) to the anterior insula (AI), posterior insula (PI), or dACC on conditioned pain modulation (CPM) and temporal summation of pain (TSP). METHODS: N = 16 volunteers underwent TSP and CPM pain tasks pre/post a 10 min LIFU intervention to either the AI, PI, dACC or Sham stimulation. Pain ratings were collected pre/post LIFU. RESULTS: Only LIFU to the PI significantly attenuated pain ratings during the TSP protocol. No effects were found for the CPM task for any of the LIFU targets. LIFU pressure modulated group means but did not affect overall group differences. CONCLUSIONS: LIFU to the PI reduced temporal summation of pain. This may, in part, be due to dosing (pressure) of LIFU. Inhibition of the PI with LIFU may be a future potential therapy in chronic pain populations demonstrating central sensitization. The minimal effective dose of LIFU for efficacious neuromodulation will help to translate LIFU for therapeutic options.
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Corteza Insular , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Corteza Insular/fisiología , Corteza Insular/diagnóstico por imagen , Dimensión del Dolor , Manejo del Dolor/métodos , Dolor , Terapia por Ultrasonido/métodos , Corteza Cerebral/fisiología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatologíaRESUMEN
This study was conducted to investigate the value of Synechococcus 7942 (Syne) as a sensitizer for photo-sonodynamic therapy (PSDT). Syne was characterized. The efficacy of Syne-mediated PSDT were verified in vitro (in 4T1 breast cancer cells) and in vivo (in a breast tumor-bearing mouse model). The safety of Syne-mediated PSDT was verified in vivo. Results indicated that Syne triggered the generation of oxygen and ROS during PSDT, thereby inducing cell death in 4T1 cells. Syne-mediated PSDT induced the death of tumor cells both in vitro and in vivo. The speed of tumor growth was delayed in animals receiving PSDT. Syne-mediated PSDT was more effective than photodynamic therapy or sonodynamic therapy alone. In addition, administration of a Syne monomer resulted in satisfactory tumor targeting. Syne-mediated PSDT affected neither the animal body weight nor the major organs, indicating satisfactory safety. Accordingly, Syne is an efficient, safe, and readily available sensitizer that is ideal for potential clinical use of PSDT to treat breast cancer. The findings of this study are useful for exploration of a novel sensitizer for PSDT, which might be a promising alternative therapy against breast cancer.
Asunto(s)
Neoplasias de la Mama , Fotoquimioterapia , Synechococcus , Terapia por Ultrasonido , Animales , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ratones , Línea Celular Tumoral , Fotoquimioterapia/métodos , Terapia por Ultrasonido/métodos , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
BACKGROUND: This scoping review aims to comprehensively review the available literature on the safety and efficacy of focused ultrasound (FUS) for blood-brain barrier disruption (BBBD) in patients with high-grade gliomas, including glioblastoma (GBM). High-grade gliomas pose significant challenges in neuro-oncology due to their aggressiveness and intricate location, often limiting the efficacy of traditional treatments. FUS offers a promising approach by transiently disrupting the blood-brain barrier, thereby facilitating enhanced drug delivery to tumor cells while minimizing systemic side effects. METHODS: A scoping review adhering to PRISMA guidelines was conducted to explore the literature on FUS-induced BBBD in glioma patients. PubMed and Embase databases were searched from inception to April 2024 using defined keywords. Original clinical studies focusing on FUS for BBBD in gliomas were included. Two reviewers independently screened records, with conflicts resolved by a third reviewer. Data extraction and quality assessment were performed accordingly. RESULTS: A total of 1,310 studies were initially identified, resulting in nine eligible studies after screening and selection. These studies, published between 2016 and 2024, included 106 patients (39.6 % female) with ages ranging from 29 to 80 years. Recurrent GBM was the most common diagnosis (100 patients), with other diagnoses including anaplastic astrocytoma, diffuse infiltrating glioma, and oligodendroglioma. Various FUS devices and microbubble contrast agents were employed across the studies. Safety and efficacy were assessed in both experimental and clinical settings, with no significant adverse events reported during BBBD procedures. Notably, BBBD facilitated enhanced drug delivery to tumor tissue, demonstrating potential therapeutic benefits. CONCLUSION: Studies investigating BBBD using FUS demonstrate promising outcomes in experimental and clinical settings. BBBD procedures in patients with malignant gliomas and recurrent GBM show safety and successful enhancement of drug delivery potential. Overall, FUS-mediated BBBD emerges as a safe and feasible approach for improving therapeutic outcomes in brain tumor patients, warranting further clinical exploration and optimization.
Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Glioma , Humanos , Glioma/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Terapia por Ultrasonido/métodosRESUMEN
Sonodynamic therapy (SDT) is a minimally invasive therapeutic approach, that uses ultrasound activating sonosensitizers to generate reactive oxygen species (ROS) for inducing the tumor cell death. However, the SDT is always limited by the dissatisfactory performance of sonosensitizers and hypoxic tumor microenvironment (TME). Nano iron oxide is a narrow bandgap semiconductor material with good biocompatibility. The doping of manganese into iron oxide (Mn-doped iron oxide nano-crystals named Mn-Fe2O3 NCs) not only reduced the band gap of iron oxide and altered the valence band position of iron oxide, but also introduced more oxygen vacancies and inhibited the complexation of electrons (e-) and holes (h+), significantly enhancing the ability to generate ROS. The Mn-Fe2O3 NCs improved the hypoxic TME by self-generating oxygen and consuming endogenous glutathione (GSH), which amplified oxidative stress and further enhanced the SDT. The therapeutic results showed that the prepared Mn-Fe2O3 NCs could efficiently inhibit the triple-negative breast cancer (TNBC) cells by SDT (80.49â¯% inhibition ratio in vivo). Overall, we propose a simple method to design inorganic sonosensitizers for enhancing efficient sonodynamic therapy.