A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

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 (•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.

Ultrasound-responsive microfibers promoted infected wound healing with neuro-vascularization by segmented sonodynamic therapy and electrical stimulation.

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.

Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

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-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % 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-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

Semiconducting polymer nanoprodrugs enable tumor-specific therapy via sono-activatable ferroptosis.

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.

Focused Ultrasound for Neurodegenerative Diseases.

Neurodegenerative diseases are a leading cause of death and disability and pose a looming global public health crisis. Despite progress in understanding biological and molecular factors associated with these disorders and their progression, effective disease modifying treatments are presently limited. Focused ultrasound (FUS) is an emerging therapeutic strategy for Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In these contexts, applications of FUS include neuroablation, neuromodulation, and/or blood-brain barrier opening with and without facilitated intracerebral drug delivery. Here, the authors review preclinical evidence and current and emerging applications of FUS for neurodegenerative diseases and summarize future directions in the field.

Guided biofilm therapy versus conventional protocol-clinical outcomes in non-surgical periodontal therapy.

BACKGROUND: The aim of the randomized controlled clinical trial study was to evaluate the effectiveness in reducing pathologically increased pocket probing depths (PPD > 3 mm) using the Guided Biofilm Therapy (GBT) protocol (adapted to the clinical conditions in non-surgical periodontal therapy (NSPT): staining, air-polishing, ultrasonic scaler, air-polishing) compared to conventional instrumentation (staining, hand curettes/sonic scaler, polishing with rotary instruments) both by less experienced practitioners (dental students). METHODS: All patients were treated according to a split-mouth design under supervision as diseased teeth of quadrants I/III and II/IV randomly assigned to GBT or conventional treatment. In addition to the treatment time, periodontal parameters such as PPD and bleeding on probing (BOP) before NSPT (T0) and after NSPT (T1: 5 ± 2 months after T0) were documented by two calibrated and blinded examiners (Ethics vote/ Trial-register: Kiel-D509-18/ DRKS00026041). RESULTS: Data of 60 patients were analyzed (stage III/IV: n = 36/ n = 24; grade A/ B/ C: n = 1/ n = 31/ n = 28). At T1, a PPD reduction of all diseased tooth surfaces was observed in 57.0% of the GBT group and 58.7% of the control group (p = 0.067). The target endpoint (PPD ≤ 4 mm without BOP) was achieved in 11.5% for GBT (conventional treatment: 11.2%; p = 0.714). With the exception for number of sites with BOP, which was at T1 15.9% in the GBT group and 14.3% in the control group (p < 0.05) no significant differences between the outcomes of the study were found. At 30.3(28.3) min, the treatment time was significantly shorter in GBT than in the control group at 34.6(24.5) min (p < 0.001). CONCLUSIONS: With both protocols (GBT/ conventional instrumentation) comparably good clinical treatment results can be achieve in NSPT in stage III-IV periodontitis patients. TRIAL REGISTRATION: The study was registered before the start of the study and can be found under the number DRKS00026041 in the German Clinical Trials Register. The registration date was 19/08/2021.

Strategically Engineered Ru(II) Complexes with Enhanced ROS Activity Enabling Potent Sonodynamic Effect against Multidrug-Resistant Biofilms.

Sonodynamic therapy (SDT) can generate reactive oxygen species (ROS) to combat multidrug-resistant biofilms, which pose significant challenges to human health. As the key to producing ROS in SDT, the design of sonosensitizers with optimal molecular structures for sufficient ROS generation and activity in complex biofilm matrix is essential. In this study, we propose a π-expansion strategy and synthesize a series of small-molecule metal Ru(II) complexes (Ru1-Ru4) as sonosensitizers (Ru1-Ru4) to enhance the efficacy of SDT. Among these complexes, Ru4 demonstrates remarkable ROS generation capability (∼65.5-fold) that surpasses most commercial sonosensitizers (1.3- to 6.7-fold). Through catalyzing endogenous H2O2 decomposition, Ru4 facilitates the production of abundant O2 as a resource for 1O2 and the generation of new ROS (i.e., •OH) for improving SDT. Furthermore, Ru4 maintains the sustained ROS activity via consuming the interferences (e.g., glutathione) that react with ROS. Due to these unique advantages, Ru4 exhibits potent biofilm eradication ability against methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo, underscoring its potential use in clinical settings. This work introduces a new approach for designing effective sonosensitizers to eliminate biofilm infections, addressing a critical need in healthcare management.

Sonodynamic Therapy for HER2+ Breast Cancer with Iodinated Heptamethine Cyanine-Trastuzumab Conjugate.

The first example of sonodynamic therapy (SDT) with a cyanine dye-antibody conjugate is reported. The aim of this study was to evaluate the sonodynamic efficacy of a trastuzumab-guided diiodinated heptamethine cyanine-based sensitizer, 2ICy7-Ab, versus its non-iodinated counterpart, Cy7-Ab, in a human epidermal growth factor receptor 2-positive (HER2+) xenograft model. In addition, the combined sonodynamic and photodynamic (PDT) effects were investigated. A single intravenous injection of 2ICy7-Ab followed by sonication or combined sonication and photoirradiation in mice resulted in complete tumor growth suppression compared with the nontreated control and showed no detectable toxicity to off-target tissues. In contrast, Cy7-Ab provided only a moderate therapeutic effect (~1.4-1.6-fold suppression). SDT with 2ICy7-Ab resulted in a 3.5-fold reduction in tumor volume within 45 days and exhibited 13-fold greater tumor suppression than PDT alone. In addition, 2ICy7-Ab showed more durable sonostability than photostability. The sonotoxicity of the iodinated versus noniodinated counterparts is attributed to the increased generation of hydroxyl radicals, superoxide, and singlet oxygen. We observed no significant contribution of PDT to the efficacy of the combined SDT and PDT, indicating that SDT with 2ICy7-Ab is superior to PDT alone. These new findings set the stage for the application of cyanine-antibody conjugates for fluorescently monitored targeted sonodynamic treatment of cancer.

2D spatiotemporal passive cavitation imaging and evaluation during ultrasound thrombolysis based on diagnostic ultrasound platform.

Acoustic cavitation plays a critical role in various biomedical applications. However, uncontrolled cavitation can lead to undesired damage to healthy tissues. Therefore, real-time monitoring and quantitative evaluation of cavitation dynamics is essential for understanding underlying mechanisms and optimizing ultrasound treatment efficiency and safety. The current research addressed the limitations of traditionally used cavitation detection methods by developing introduced an adaptive time-division multiplexing passive cavitation imaging (PCI) system integrated into a commercial diagnostic ultrasound platform. This new method combined real-time cavitation monitoring with B-mode imaging, allowing for simultaneous visualization of treatment progress and 2D quantitative evaluation of cavitation dosage within targeted area. An improved delay-and-sum (DAS) algorithm, optimized with a minimum variance (MV) beamformer, is utilized to minimize the side lobe effect and improve the axial resolution typically associated with PCI. In additional to visualize and quantitatively assess the cavitation activities generated under varied acoustic pressures and microbubble concentrations, this system was specifically applied to perform 2D cavitation evaluation for ultrasound thrombolysis mediated by different solutions, e.g., saline, nanodiamond (ND) and nitrogen-annealed nanodiamond (N-AND). This research aims to bridge the gap between laboratory-based research systems and real-time spatiotemporal cavitation evaluation demands in practical uses. Results indicate that this improved 2D cavitation monitoring and evaluation system could offer a useful tool for comprehensive evaluating cavitation-mediated effects (e.g., ultrasound thrombolysis), providing valuable insights into in-depth understanding of cavitation mechanisms and optimization of cavitation applications.

Systematic narrative review of modalities in physiotherapy for managing pain in hip and knee osteoarthritis: A review.

Osteoarthritis (OA) affects 528 million individuals globally, predominantly in knee and hip joints, with a notable impact on females aged over 55, resulting in a substantial economic burden. However, the efficacy of modalities used in physiotherapy to manage OA pain for reducing the need for joint replacement remains an open question, and guidelines differ. Our systematic narrative review, drawing from reputable databases (e.g., PubMed, Cochrane, and CINAHL) with specific Mesh terms investigated evidence from 23 Randomized Controlled Trials (that included a control or a sham group in 30 different protocols) using therapeutic modalities like ultrasound, diathermy, and electrical stimulation for knee and hip OA pain, involving a total of 1055 subjects. We investigated the attainment of minimal clinically important differences in pain reduction, operationalized through a 20% decrement in the Western Ontario and McMaster University Arthritis Index or Visual Analog Scale (VAS) score. Our results indicated that 15 protocols out of 30 reach that level, but there were no statistical differences among modalities. Half of the protocol presented in the literature reached clinical efficiency but studies on hip remains scarce. We recommend a comprehensive, sequential, and multimodal intervention plan for individuals with joint OA with initial transcutaneous electrical nerve stimulation and progressing to a 2-week protocol of continuous ultrasound, potentially combined with deep microwave diathermy. Long-term intervention involves the use of pulsed electrical stimulation. For hip OA, a cautious approach and discussions with healthcare providers about potential benefits of spinal cord nerve stimulation.

Nanobubble-mediated co-delivery of siTRIM37 and IR780 for gene and sonodynamic combination therapy against triple negative breast cancer.

Gene therapy often fails due to enzyme degradation and low transfection efficiency, and single gene therapy usually cannot completely kill tumor cells. Several studies have reported that tripartite motif-containing protein 37 (TRIM37) plays a significant role in promoting the occurrence and development of triple negative breast cancer (TNBC). Herein, we constructed siTRIM37 and IR780 co-loaded nanobubbles (NBs) to achieve the combination of gene therapy and sonodynamic therapy (SDT) against TNBC. On the one hand, ultrasound irradiation causes siRNA@IR780 NBs rupture to produce ultrasound targeted NB destruction effect, which promotes the entry of IR780 and siTRIM37 into cells, increasing the local concentration of IR780 and gene transfection efficiency. On the other hand, under the stimulation of ultrasound, IR780 generates reactive oxygen species to kill TNBC cells. Mechanism studies reveal that TRIM37 is an anti-apoptotic gene in TNBC, and inhibiting TRIM37 expression can induce cell death through the apoptotic pathway. And the combination of siTRIM37 and SDT can aggravate the degree of apoptosis to increase cell death. Therefore, siRNA@IR780 NBs-mediated combination therapy may provide a new treatment approach for TNBC in the future.

Unilateral acute cataract after facial aesthetic procedure: a case report.

Aging and face sagging have many causes, and various techniques are used for treatment, including noninvasive procedures, such as focused ultrasound, which uses the principle of collagen regeneration by coagulative necrosis of the dermis layers using radiofrequency, but this procedure has complications. We reported a case of a 54-year-old female patient who complained of poor visual acuity in her right eye three days after a focused ultrasound facial aesthetic procedure, with the best visual acuity of 20/60. Biomicroscopy of the right eye revealed an acute cataract with three points of fibrosis extending from the posterior to the anterior capsule. The patient underwent phacoemulsification surgery with visual rehabilitation and improved vision of 20/20. We hypothesized that the occurrence of acute cataract was related to the inappropriate use of focused ultrasound.

A review of sonodynamic therapy for brain tumors.

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.

Biodegradable oxygen-evolving metalloantibiotics for spatiotemporal sono-metalloimmunotherapy against orthopaedic biofilm infections.

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.

Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

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.

Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis.

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.

Bioactive Nanoliposomes for Enhanced Sonodynamic-Triggered Disulfidptosis-Like Cancer Cell Death via Lipid Peroxidation.

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.

ZnO quantum dots decorated BaTiO3 for cancer sonodynamic therapy.

Sonodynamic therapy depending on ultrasound irradiation, which generates reactive species to kill cancer cells, has attracted considerable attention due to the deep tissue penetration depth. However, the insufficient separation of electron/hole pairs induces its limited therapeutic efficiency. Herein, we use oxygen vacancy and ZnO quantum dots decoration techniques to enhance electron/hole separation and reactive species production. In oxygen vacancy-engineered BaTiO3, the higher oxygen vacancy concentration leads to more efficient adsorption of activate O2 and thus results in production of more radicals. In BaTiO3/ZnO heterostructures, the built-in electric field further improves separation of electron/hole pairs. The separated electron/hole react with O2/H2O to produce reactive species of •OH/∙O2- and kill cancer cells upon ultrasound irradiation. The work provides a guidance for sonosensitizers to tumor therapy.