Newly developed gas-assisted sonodynamic therapy in cancer treatment

Sonodynamic therapy (SDT) is an emerging noninvasive treatment modality that utilizes low-frequency and low-intensity ultrasound (US) to trigger sensitizers to kill tumor cells with reactive oxygen species (ROS). Although SDT has attracted much attention for its properties including high tumor specificity and deep tissue penetration, its anticancer efficacy is still far from satisfactory. As a result, new strategies such as gas-assisted therapy have been proposed to further promote the effectiveness of SDT. In this review, the mechanisms of SDT and gas-assisted SDT are first summarized. Then, the applications of gas-assisted SDT for cancer therapy are introduced and categorized by gas types. Next, therapeutic systems for SDT that can realize real-time imaging are further presented. Finally, the challenges and perspectives of gas-assisted SDT for future clinical applications are discussed.

Anti-tumor Mechanism of Sonodynamic Combined with Hyperthermia and Its Application in Tumor / 肿瘤防治研究

Sonodynamic therapy (SDT) is a new non-invasive treatment method that uses a combination of sono-sensitizers and low-intensity ultrasound (US) to treat malignant tumors. SDT is developed from photodynamic therapy (PDT). Because ultrasound can be transmitted deeper than light in tissues, sonosensitizers can be induced to be targeted, and sonosensitizers can be monitored in real time through ultrasound, SDT has significant advantages of locating the tumor site and activating the sensitizing agent in deep tissues. Therefore, compared with PDT, SDT can be used to treat tumors that are wider, deeper and more inaccessible. Hyperthermia (HT), as an adjuvant therapy, is applied to various established cancer treatments. Its mechanism is to increase the temperature of the tumor-bearing tissue to 40℃-43℃ to cause irreversible damage. This article reviews the cell signal regulation mechanism involved in SDT and HT in tumor therapy and the application progress of SDT-HT combination therapy on tumor.

Recent progress in sono-photodynamic cancer therapy: From developed new sensitizers to nanotechnology-based efficacy-enhancing strategies

Many sensitizers have not only photodynamic effects, but also sonodynamic effects. Therefore, the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT) using sensitizers for sono-photodynamic therapy (SPDT) provides alternative opportunities for clinical cancer therapy. Although significant advances have been made in synthesizing new sensitizers for SPDT, few of them are successfully applied in clinical settings. The anti-tumor effects of the sensitizers are restricted by the lack of tumor-targeting specificity, incapability in deep intratumoral delivery, and the deteriorating tumor microenvironment. The application of nanotechnology-based drug delivery systems (NDDSs) can solve the above shortcomings, thereby improving the SPDT efficacy. This review summarizes various sensitizers as sono/photosensitizers that can be further used in SPDT, and describes different strategies for enhancing tumor treatment by NDDSs, such as overcoming biological barriers, improving tumor-targeted delivery and intratumoral delivery, providing stimuli-responsive controlled-release characteristics, stimulating anti-tumor immunity, increasing oxygen supply, employing different therapeutic modalities, and combining diagnosis and treatment. The challenges and prospects for further development of intelligent sensitizers and translational NDDSs for SPDT are also discussed.

Application progresses of photodynamic and sonodynamic therapy for malignant gynecologic neoplasms / 中国医学影像技术

The incidence of gynecological malignant tumors is increasing year by year, posing serious threatens to women's health. Photoacoustic dynamic therapy includes photodynamic therapy and sonodynamic therapy, killing tumor cells by photosensitizer and sonosensitizer activated by light or ultrasound, have the advantages of non-invasion, precise targeting, little side effects and widely used in diagnosis and treatment of gynecological tumors. The progress of photoacoustic dynamic therapy and its application in cervical cancer, ovarian cancer and endometrial cancer were reviewed in this article.

Synergistic Anti-tumor Mechanisms of Low-frequency Ultrasound-targeted Microbubble Destruction:Mechanisms and Application / 中国医学科学院学报

Ultrasound contrast agent microbubbles combined with low frequency ultrasound named as low-frequency ultrasound-targeted microbubble destruction technology has become an effective and non-invasive anti-tumor therapy for deep tumors.It can enhance the efficacies of chemotherapy,gene therapy,immunotherapy,and anti-angiogenic therapy by improving cell membrane permeability and destroying tumor neovasculature.It can be applied to sonodynamic therapy and realize multimodal synergistic therapy on the basis of nanoparticles,which increases the anti-tumor efficiency and offers a promising target therapy for tumors.

Research progress of sonodynamic therapy in the field of stomatology / 口腔疾病防治

@#Sonodynamic therapy (SDT) is a cutting-edge method for the biological effects of ultrasound combined with sound-sensitive agents. In recent years, SDT has been a concern of experts and scholars in the oral field, and a series of experimental studies has been carried out. We will introduce the progress of SDT in the field of stomatology from three aspects: the therapeutic mechanism of SDT, the application of SDT in the oral field, and the current situation and future of SDT in the treatment of oral diseases. It is currently believed that singlet oxygen theory, cavitation effects, and induction of apoptosis are the main therapeutic mechanisms. The research of SDT on oral disease prevention mainly focuses on oral tumors (especially squamous cell carcinoma and osteosarcoma) and infectious diseases (such as periodontitis, maxillofacial infection, and oral mucosal disease). Although the current research is still in the experimental stage, with the continuous exploration of sonosensitizers and nanotechnology, SDT will provide great help for the clinical prevention and treatment of oral diseases in the future.

Experimental study of hematoporphyrinmonomethyl ether based PLGA nanoparticles for photoacoustic imaging-guided sonodynamic therapy / 中国医学影像技术

Objective To prepare hematoporphyrinmonomethyl ether (HMME) based poly (lactic-co-glycolic acid) (PLGA) nanoparticles, and to investigate their enhancement effect on photoacoustic (PA) imaging and sonodynamic therapy (SDT) efficacy in vitro. Methods HMME-based PLGA (HMME@PLGA) nanoparticles were synthesized using a facile double emulsion strategy. The characteristics and enhanced PA imaging capability were observed in vitro. Upon ultrasound irradiation, the reactive oxygen species (ROS) generated with MDA-MB-231 cells up-taken HMME@PLGA was investigated using flow cytometry. SDT efficacy on cellular level was further investigated. Results The fabricated HMME@PLGA nanoparticles were demonstrated with homogenized size and distribution, and the average diameter was (333.67±17.50)nm. The Zeta potential was (-10.57±1.98)mV. The encapsulation efficiency of HMME in HMME@PLGA was 75.62%, and the drug loading was 2.90%. When incubation with HMME@PLGA nanoparticles (1 mg/ml) for 24 h, the viability of MDA-MB-231 cells was 87.21%. PA signal intensities increased with the increase of HMME@PLGA concentration in vitro. Upon ultrasound irradiation, ROS was produced in MDA-MB-231 cells with the assistance of HMME@PLGA nanoparticles, further leading to cytotoxic effects and cellular death which showed obvious red fluorescence stained with Calcein-AM/PI. Meanwhile, the lysosomes structures of the dead cells disappeared when stained by acridine orange. Conclusion HMME@PLGA nanoparticles are successfully fabricated and can achieve PA imaging-guided SDT.

Investigating the Sonodynamic-Radiosensitivity Effect of Gold Nanoparticles on HeLa Cervical Cancer Cells

BACKGROUND: In this article, we estimated the combined effect of radiotherapy (RT) with ultrasound (US) wave and the ability of gold nanoparticles (GNPs) to improve their combined therapeutic effects. METHODS: At first, HeLa cells received the various treatment modalities: RT (6 MV; 0.5, 1, and 2 Gy), US irradiation (1 MHz; 0.5, 1, and 1.5 W/cm2, 1 minute), and RT+US. Afterwards, the enhanced effect of US on RT was evaluated. Then, the effect of the synthesized GNPs at different concentrations (0.2, 1, and 5 µg/mL, 24 hours) was evaluated to assess the effect on HeLa cells combined with RT+US. Cell survival rates in the different treatment groups at 24, 48, and 72 hours post-treatment were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. RESULTS: Our results show US irradiation could enhance the effect of RT at the same radiation dose and could be utilized as a sensitizer agent for RT. Moreover, our findings indicate RT+US in combination with different nanoparticle concentrations could enhance the effect of RT+US so that they can improve the treatment results up to 9.93 times and act as sonodynamic-radiosensitivity. These results also indicate that the combination of RT with US along with GNPs has synergistic effects compared to RT or US alone. Cell survival results show that combining the low US waves (1.5 W/cm2), GNPs (5 μg/mL), and X-rays (2 Gy) increase the cytotoxicity on HeLa cell up to 95.8%. CONCLUSION: We concluded that GNPs could act as a good sensitizing agent in RT+US irradiation and could result in the synergistic effects.

Advance on anti-tumor activities of sinoporphyrin sodium / 第二军医大学学报

Photodynamic therapy (PDT) is a new oncotherapy method. Photosensitizer and matched-light are the key elements of PDT. As a next generation photosensitizers of high purity, sinoporphyrin sodium (DVDMS) has the characteristics of clear structure and high content, low effective dose, short time avoiding light after treatment and good safety. Due to the discovery of ultrasonic sensitivity of DVDMS, great progresses have been made on the research and application of DVDMS-mediated sonodynamic therapy. Research suggests that DVDMS has potentials to be used for anti-tumor, anti-bacterial, treatment of psoriasis, development of therapeutic diagnostic reagents and so on. This review sums up the anti-tumor activities and mechanisms of DVDMS.

Construction and evaluation of charge-reversal nanocarrier loaded with hematoporphyrin monomethyl ether / 药学学报

Charge-reversal nanocarrier was constructed to enhance lysosomal escape and improve an-titumor effect. We synthesized the cholesterol-polyethyleneimine-hexahydrophthalic anhydride (Chol-PEI-HHPA) polymer and characterized by 1H NMR. The charge-reversal liposomes (Lipo-HHPA) were synthesized and the hematoporphyrin monomethyl ether (HMME) was loaded. pH-triggered charge conversion was determined at different pH values. The lysosomal escape and cytotoxicity of the Lipo-HHPA were evaluated in MCF-7 cells. The Lipo-HHPA was uniform with an average particle size of 102 nm. Upon the irradiation of ultrasound, burst release of HMME could be observed. The zeta potential of Lipo-HHPA changed sharply from negative (-23.5 mV) to positive (+21.2 mV) over the pH range of 7.4-4.5. In the cellular uptake experiment, the lysosomal escape of Lipo-HHPA was observed. HMME loaded Lipo-HHPA displayed obviously enhanced cytotoxicity towards MCF-7 cells. These results indicate that the charge-reversal liposomes hold a great potential in improving the cytotoxicity and antitumor effect.

Dual-modality imaging-guided sonodynamic therapy with DVDMS-Mn-loaded liposomes / 中华核医学与分子影像杂志

Objective To fabricate DVDMS-Mn-LPs and evaluate its potential on fluorescence mo-lecular imaging, MRI and sonodynamic therapy ( SDT) . Methods DVDMS was used to chelate with Mn2+, and then encapsulated into nanoliposomes by a typical thin-film rehydration method to fabricate DVDMS-Mn-LPs. The particle morphology, average diameter, zeta potential, encapsulation efficiencies and Mn2+content were determined. Fluorescence molecular imaging was performed on different concentrations of DVDMS-Mn-LPs (0, 40, 80, 120, 160 μg/ml) with the small animal fluorescence imaging system. T1WI was per-formed with 3.0 T MR. The SDT effect of DVDMS-Mn-LPs was verified by CCK8 assay among the following groups:control group, ultrasound group ( experimental group 1, EG1) , DVDMS-Mn-LPs group ( EG2) and DVDMS-Mn-LPs + ultrasound group ( EG3) . One-way analysis of variance and the least significant differ-ence t test were used to analyze the data. Results DVDMS-Mn-LPs exhibited a well-defined spherical mor-phology and homogeneous distribution. The encapsulation efficiency was (65.56±1.47)%. ICP-AES meas-urement revealed that the chelation of Mn2+ with DVDMS occurred at a molar ratio of 1. 6:1. The fluores-cence intensities progressively increased with the elevated concentrations of DVDMS-Mn-LPs. The r1 value for DVDMS-Mn-LPs was 23.74 mmol·L-1·s-1. The cell viabilities of EG3 was (54.82±8.55)%, which were significantly lower than those of EG2 and EG1 ((86.54±2.67)% and (83.76±6.48)%;F=6011, t values: -8.35, -9.15, all P<0.001). Conclusion DVDMS-Mn-LPs is successfully fabricated and has good potential on fluorescence molecular imaging, MRI and SDT, which provides a promising imaging-guided modality for glioma treatment in vivo.

Research on status and application prospects of sonodynamic therapy with intermediate frequency low-intensity ultrasound used to treat endometrial disease / 中国医学装备

Sonodynamic therapy in many treatment methods of tumors, is a relatively new approach. Sonodynamic therapy as a treatment method is developed on the basis of photodynamic therapy. Compared to the lightwave, the ability to penetrate mammalian tissue of ultrasound is stronger. So sonodynamic therapy is a more promising therapeutic area. Many scholars have explored the clinical applications of sonodynamic therapy, and progress has been made in many areas. Because the female genitalia is connected the outside of body, it is more conducive that Sonodynamic therapy play a partial role. Sonodynamic therapy has some progress in the application of gynecology, and we hope it would have more progress in the treatment of endometrial disease.

Effects of HMME-SDT on hypertrophic scar of rabbit ear / 中华医学美学美容杂志

Objective To observe the clinical efficacy of HMME-SDT therapy for the treatment of hypertrophic scar (HS) of rabbit ear.Methods 60 white rabbits were randomly divided into five groups.The model group and HMME-SDT treatment group were used to establish the models of hypertrophic scar in ears.Results The effect of HMME-SDT on the fibroblastic density in the hypertrophic scarring models was observed in rabbit ears.The HMME-SDT could lower the fibroblastic density,compared with the model group,with significant difference (P＜ 0.05).The effect of HMME-SDT on the collagen area density was noted in the hypertrophic scarring models in rabbit ears.The HMME-SDT could lower the collagen area density,compared with the model group,with significant difference from the fourth week of the epithelialization (P＜0.01).Conclusions HMME is an effective sonosensitizer.HMME-SDT can significantly inhibit hypertrophic scar of rabbit ear.

Effect of sonodynamic therapy on H22 tumor-bearing mice using hematoporphyrin-loaded PLGA ultrasound contrast agents / 中国医学影像技术

Objective To study the treatment effect on H22 tumor-bearing mice using ultrasound (US) combined with hematoporphyrin-loaded PLGA ultrasound contrast agents (HP-PLGA). Methods Hematoporphyrin-loaded PLGA ultrasound contrast agents were prepared using the technique of double emulsion, and the properties of the contrast agents were detected. Then 30 H22 tumor-bearing mice were averagely divided into 5 groups for different treatment. The growth curve of H22 tumor was depicted within 15 days after treatment. The inhibition rate of tumor quality on the 15th day and the index about apoptosis and proliferation on tumor of each group were measured, respectively. Results Self-made hematoporphyrin-loaded PLGA ultrasound contrast agents had mean size of 602.3 nm with encapsulation efficiency of 63.50% and drug loading of 2.15%. After treatment, tumors of the E group (US+HP-PLGA) grew most slowly compared with other groups. The inhibition rate of tumor quality and the apoptotic index in E group were significantly higher than those in other four groups (P＜0.05), while the proliferation index in E group was significantly lower than that in other groups (P＜0.05). Conclusion Ultrasound combined with hematoporphyrin-loaded PLGA ultrasound contrast agents could inhibit growth and promote the apoptosis of H22 tumor in mice, providing a novel strategy for sonodynamic therapy on the tumor.

Photodynamic Therapy and Sonodynamic Therapy / 中国医学物理学杂志

Objective: This paper summarized the research status and progress of photodynamic therapy (PDT) and sonodynam-ic therapy (SDT), and we hope this can be a useful reference for clinics or research. Methods: In this review we expound their molecular mechanisms in detail and classify the photosensitizer and sonosensitizer, indicate their applications for the cancer treatment and summarize their new treating modes. PDT and SDT have huge potential for cancer treatment. Results: PDT and SDT have achieved a certain results, whereas there are still many problems, such as tissue oxygen content, new photosensitizer and sonosensitizer, drug dosage and mechanisms of SDT. Conclusions: PDT and SDT, which are new methods for treating cancer, have shown a good application prospect. But PDT has not been universal in clinics and SDT is still in the experiment stage.