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).

Bimetal-Biligand Frameworks for Spatiotemporal Nitric Oxide-Enhanced Sono-Immunotherapy.

Sonodynamic therapy can trigger immunogenic cell death to augment immunotherapy, benefiting from its superior spatiotemporal selectivity and non-invasiveness. However, the practical applications of sonosensitizers are hindered by their low efficacy in killing cancer cells and activating immune responses. Here, two US Food and Drug Administration-approved drug ligands (ferricyanide and nitroprusside) and two types of metals (copper/iron) are selected to construct a bimetal-biligand framework (Cu[PBA-NO]). Through elaborate regulation of multiple metal/ligand coordination, the systemically administered Cu[PBA-NO] nanoagent shows sono-catalytic and NO release ability under ultrasound irradiation, which can be used for effective sono-immunotherapy. Moreover, Cu[PBA-NO] can downregulate intracellular glutathione levels that would destroy intracellular redox homeostasis and facilitate reactive oxygen species accumulation. The released tumor-associated antigens subsequently facilitate dendritic cell maturation within the tumor-draining lymph node, effectively initiating a T cell-mediated immune response and thereby bolstering the capacity to identify and combat cancer cells. This study paves a new avenue for the efficient cancer sono-immunotherapy.

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.

An Oxidative Stress Nano-Amplifier for Improved Tumor Elimination and Combined Immunotherapy.

Amplifying oxidative stress to disrupt intracellular redox homeostasis can accelerate tumor cell death. In this work, an oxidative stress amplifier (PP@T) is prepared for enhanced tumor oxidation therapy to reduce tumor growth and metastases. The nano-amplifier has been successfully constructed by embedding MTH1 inhibitor (TH588) in the PDA-coated porphyrin metal-organic framework PCN-224. The controllable-released TH588 is demonstrated from pores can hinder MTH1-mediated damage-repairing process by preventing the hydrolysis of 8-oxo-dG, thereby amplifying oxidative stress and exacerbating the oxidative DNA damage induced by the sonodynamic therapy of PP@T under ultrasound irradiation. Furthermore, PP@T can effectively induce immunogenic cell death to trigger systemic anti-tumor immune response. When administered in combination with immune checkpoint blockade, PP@T not only impedes the progression of the primary tumor but also achieves obvious antimetastasis in breast cancer murine models, including orthotopic and artificial whole-body metastasis models. Furthermore, the nanoplatform also provides photoacoustic imaging for in vivo treatment guidance. In conclusion, by amplifying oxidative stress and reactive oxygen species sensitized immunotherapy, this image-guided nanosystem shows potential for highly specific, effective combined therapy against tumor cells with negligible side-effects to normal cells which will provide a new insight for precise tumor treatment.

Bi-Pt Heterojunction Cascade Reaction Platform for Sono-Immunotherapy of Tumors via PANoptosis and Ferroptosis.

Sonodynamic therapy (SDT) represents a promising, noninvasive, and precise treatment modality for tumors, demonstrating significant potential in clinical applications. However, the efficiency of sonosensitizers in generating reactive oxygen species (ROS) is often limited by rapid electron-hole recombination. In this study, BiF3@BiOI is synthesized via a co-precipitation method, followed by in-situ reduction to decorate it with Pt nanoparticles, resulting in BiF3@BiOI@Pt-PVP (BBP) nanocomposite for enhancing SDT efficacy. The formation of the BiF3@BiOI heterojunction enhances charge separation ability. The decoration of Pt nanoparticles narrows the bandgap and alters the band positions and Fermi level of BBP, which can effectively mitigate the rapid recombination of electron-hole pairs and facilitate a cascade reaction of ROS, thereby improving ROS generation efficiency with ultrasound excitation. Additionally, bismuth ions in BBP and the generated holes consume glutathione, exacerbating cellular oxidative damage, and triggering PANoptosis and ferroptosis. Furthermore, Pt nanoparticles demonstrate peroxidase-like activity, catalyzing endogenous hydrogen peroxide to oxygen. These functions are helpful against tumors for alleviating hypoxic conditions, reshaping the microenvironment, modulating immune cell infiltration capacity, and enhancing the efficacy of immunotherapy. The dual strategy of forming heterojunctions and sensitization with noble metals effectively enhances the efficacy of sono-catalytic therapy-induced immune activation in tumor treatment.

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.

MR-guided focused ultrasound in pediatric neurosurgery: current insights, technical challenges, and lessons learned from 45 treatments at Children's National Hospital.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is an evolving technology with numerous present and potential applications in pediatric neurosurgery. The aim of this study was to describe the use of MRgFUS, technical challenges, complications, and lessons learned at a single children's hospital. METHODS: A retrospective analysis was performed of a prospectively collected database of all pediatric patients undergoing investigational use of MRgFUS for treatment of various neurosurgical pathologies at Children's National Hospital. Treatment details, clinical workflow, and standard operating procedures are described. Patient demographics, procedure duration, and complications were obtained through a chart review of anesthesia and operative reports. RESULTS: In total, 45 MRgFUS procedures were performed on 14 patients for treatment of diffuse intrinsic pontine glioma (n = 12), low-grade glioma (n = 1), or secondary dystonia (n = 1) between January 2022 and April 2024. The mean age at treatment was 9 (range 5-22) years, and 64% of the patients were male. With increased experience, the total anesthesia time, sonication time, and change in core body temperature during treatment all significantly decreased. Complications affected 4.4% of patients, including 1 case of scalp edema and 1 patient with a postprocedure epidural hematoma. Device malfunction requiring abortion of the procedure occurred in 1 case (2.2%). Technical challenges related to transducer malfunction and sonication errors occurred in 6.7% and 11.1% of cases, respectively, all overcome by subsequent user modifications. CONCLUSIONS: The authors describe the largest series on MRgFUS technical aspects in pediatric neurosurgery at a single institution, comprising 45 total treatments. This study emphasizes potential technical challenges and provides valuable insights into the nuances of its application in pediatric patients.

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.

A Fully Integrated Conformal Wearable Ultrasound Patch for Continuous Sonodynamic Therapy.

Cancer treatment is a continuous process, that the current therapy cannot meet the requirement well, including radiotherapy and chemotherapy. Wearable ultrasound device has the potential for continuous sonodynamic therapy due to its portability. However, the miniaturization of ultrasonic probe, system integration of device, and the strategy of continuous treatment are still urgent issues to be addressed. Herein, a portable wearable antitumor system is introduced, which utilizes a custom-developed multiplexed ultrasonic patch array (CWUS Patch) to accurately focus ultrasound on the lesion site and controllably stimulate sonosensitizer to produce a large amount of toxic reactive oxygen species (ROS). The system enables dynamic control of the ultrasound patches and allows real-time adjustments to optimize their performance in various applications, providing greater flexibility and precision in healthcare technology. Furthermore, the excellent penetration property of ultrasound into tumor tissues that induce synchronous apoptosis of tumor cells from the inside out is verified through a mouse model of breast cancer. This fully integrated conformal wearable ultrasound system provides a promising approach to noninvasively, continuously, and efficiently treat deep tumors.

Recent Progress in Photothermal, Photodynamic and Sonodynamic Cancer Therapy: Through the cGAS-STING Pathway to Efficacy-Enhancing Strategies.

Photothermal, photodynamic and sonodynamic cancer therapies offer opportunities for precise tumor ablation and reduce side effects. The cyclic guanylate adenylate synthase-stimulator of interferon genes (cGAS-STING) pathway has been considered a potential target to stimulate the immune system in patients and achieve a sustained immune response. Combining photothermal, photodynamic and sonodynamic therapies with cGAS-STING agonists represents a newly developed cancer treatment demonstrating noticeable innovation in its impact on the immune system. Recent reviews have concentrated on diverse materials and their function in cancer therapy. In this review, we focus on the molecular mechanism of photothermal, photodynamic and sonodynamic cancer therapies and the connected role of cGAS-STING agonists in treating cancer.

[Salphen-Based Fe-N2O2@C Nanomaterial Applied in Synergistic Sonodynamic and Chemodynamic Therapy of Tumors]. / 基于Salphen结构的Fe-N2O2@C材料用于声动力协同化学动力治疗肿瘤.

Objective: To synthesize a Salphen-based Fe-N2O2@C material with high peroxidase (POD)-mimicking activity and sonosensitivity for the synergistic sonodynamic (SDT) and chemodynamic (CDT) therapy of tumors. Methods: Fe-N2O2 was synthesized via the hydrothermal method, and Fe-N2O2@C was prepared by incorporating a ketjen black substrate. The morphology, structure, composition, enzyme mimic activity for reactive oxygen species (ROS) production, and sonosensitivity of the material were characterized. The ability and mechanism of Fe-N2O2@C to perform synergistic SDT and CDT killing of 4T1 mouse breast cancer cells were explored through in vitro experiments. The in vivo tumor-killing ability of Fe-N2O2@C combined with ultrasound irradiation was investigated using a subcutaneous 4T1 tumor-bearing mouse model. Results: FFe-N2O2 and Fe-N2O2@C were both irregularly shaped nanospheres with average particle sizes of 25.9 nm and 36.2 nm, respectively. XRD, FTIR, and XPS analyses confirmed that both Fe-N2O2 and Fe-N2O2@C possessed a Salphen covalent organic framework structure with M-N2O2 coordination, and the ketjen black loading had no significant impact on this structure. Compared to Fe-N2O2, Fe-N2O2@C exhibited high POD-mimicking activity (with K m reduced from 19.32 to 5.82 mmol/L and v max increased from 2.51×10-8 to 8.92×10-8 mol/[L·s]) and sonosensitivity. Fe-N2O2@C in combination with ultrasound irradiation could produce a large amount of ROS within cells and a subsequent significant decrease in mitochondrial membrane potential, thereby inducing TEM-observable mitochondrial damage and causing cell apoptosis and death. In addition, in vivo experiments showed that Fe-N2O2@C in combination with ultrasound irradiation could effectively inhibit tumor growth in a 4T1 subcutaneous tumor-bearing mouse model without significant in vivo toxicity. Conclusion: In this study, we prepared a Salphen-based Fe-N2O2@C material with good biocompatibility, which can be used in combination with ultrasound irradiation to achieve SDT and CDT synergistic killing of tumor cells and inhibit tumor growth. This Salphen-based Fe-N2O2@C nanomaterial shows promising potential for multimodal tumor therapy.

Multi-modal triggered-release sonodynamic/chemo/phototherapy synergistic nanocarriers for the treatment of colon cancer.

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100 nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

Ultrasound-Sensitive Targeted Liposomes as a Gene Delivery System for the Synergistic Treatment of Hepatocellular Carcinoma.

Gene therapy and sonodynamic therapy, as emerging treatment methods, have great potential in cancer treatment. However, there are significant challenges in the in vivo delivery of genes and sonosensitizers during the treatment process, which ultimately affects the therapeutic outcome. In this study, an ultrasound-sensitive targeted liposome nanoparticle system (MLipsiBcl-2) is developed to deliver the sonosensitizers and siRNA for the synergistic treatment of hepatocellular carcinoma. Generation of reactive oxygen species (ROS) by MLipsiBcl-2 can be initiated through ultrasound stimulation, leading to liposome rupture and release of the sonosensitizer and small interfering RNA (siRNA). Furthermore, ROS can disrupt lysosomal membranes, facilitating gene release for downregulating overexpressed antiapoptotic protein levels in cancer cells. Experimental results from in vitro and in vivo studies demonstrated the efficacy of synergistic treatment on hepatocellular carcinoma cells and the high biocompatibility of MLipsiBcl-2 under ultrasound stimulation. The advancement of this ultrasound-sensitive targeted gene delivery system shows potential as a versatile therapeutic platform that is easily operable, presenting a prospect for a synergistic treatment approach across various cancer types.

Combined UTMD-Nanoplatform for the Effective Delivery of Drugs to Treat Renal Cell Carcinoma.

Introduction: The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC). Methods: ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle's multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo. Results: The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry. Conclusion: ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.

Oxygen-carrying semiconducting polymer nanoprodrugs induce sono-pyroptosis for deep-tissue tumor treatment.

Sonodynamic therapy (SDT) has been explored for cancer therapy, especially for deep tumors due to its low tissue penetration restriction. The therapeutic efficacy of SDT is limited due to the complicated tumor microenvironment. This study reports the construction of oxygen-carrying semiconducting polymer nanoprodrugs (OSPNpro) for deep tumor treatment via combining amplified SDT with pyroptosis. An oxygen carrier perfluorohexane, sonodynamic semiconducting polymer as the sonosensitizer, and reactive oxygen species (ROS)-responsive prodrug are co-loaded into a nanoparticle system, leading to the formation of these polymer nanoprodrugs. Such OSPNpro show an effective accumulation in tumor tissues after systemic administration, in which they deliver oxygen to relieve tumor hypoxia microenvironment and thus mediate amplified SDT via producing ROS under ultrasound (US) irradiation, even when the tumors are covered with a 2-cm chicken breast tissue. In addition, the ROS-responsive prodrugs are activated by the generated ROS to trigger pyroptosis of tumor cells. Such a sono-pyroptosis induces a strong antitumor immunity with obviously higher level infiltrations of effector immune cells into tumors. Therefore, OSPNpro-based combinational therapy can greatly inhibit the growth of 2-cm chicken breast tissue-covered deep tumors and suppress tumor metastasis. This study offers a prodrug nanoplatform for treatment of deep tumor via sono-pyroptosis strategy.

Application progress of nanomaterials in the treatment of prostate cancer.

Prostate cancer is one of the most common malignant tumors in men, which seriously threatens the survival and quality of life of patients. At present, there are serious limitations in the treatment of prostate cancer, such as drug tolerance, drug resistance and easy recurrence. Sonodynamic therapy and chemodynamic therapy are two emerging tumor treatment methods, which activate specific drugs or sonosensitizers through sound waves or chemicals to produce reactive oxygen species and kill tumor cells. Nanomaterials are a kind of nano-scale materials with many excellent physical properties such as high targeting, drug release regulation and therapeutic monitoring. Sonodynamic therapy and chemodynamic therapy combined with the application of nanomaterials can improve the therapeutic effect of prostate cancer, reduce side effects and enhance tumor immune response. This article reviews the application progress of nanomaterials in the treatment of prostate cancer, especially the mechanism, advantages and challenges of nanomaterials in sonodynamic therapy and chemodynamic therapy, which provides new ideas and prospects for research in this field.

Vacancy-engineered Mn-doped iron oxide nano-crystals for enhanced sonodynamic therapy through self-supplied oxygen.

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 (80.49 % inhibition ratio in vivo). Overall, we propose a simple method to design inorganic sonosensitizers for enhancing efficient sonodynamic therapy.

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.

The advance of ultrasound-enabled diagnostics and therapeutics.

Point-of-care ultrasound demonstrates significant potential in biomedical research due to its noninvasive, real-time visualization, cost-effectiveness, and other biological benefits. Ultrasound irradiation can precisely control the mechanical and physicochemical effects on pathogenic lesions, enabling real-time visualization, tunable tissue penetration depth, and therapeutic applications. This review summarizes recent advancements in ultrasound-enabled diagnostics and therapeutics, focusing on mechanochemical effects that can be directly integrated into biomedical applications. Additionally, the structure-functionality relationships of sonotheranostic nanoplatforms are systematically discussed, providing insights into the underlying biological effects. Finally, the limitations of current ultrasonic medicine are discussed, along with potential expansions to facilitate patient-centered translations.

Evaluation of the value of Synechococcus 7942 as a sensitizer for photo-sonodynamic therapy against breast cancer.

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.