Methylene blue-enhanced photodynamic and sonodynamic therapy againstStaphylococcus aureus: From laboratory research to clinical evaluation.

Introduction: Photodynamic therapy is a noninvasive therapeutic method for tumors with a maximum depth of 5 mm. On the other hand, most photosensitizers are also susceptible to ultrasound waves (the basis of sonodynamic therapy). Therefore, it is expected that a combination of the two therapeutic methods will increase effectiveness of photodynamic therapies for lower doses of sensitizer and curing deeper tumors. This study evaluates the synergistic effects of photodynamic and sonodynamic therapies. Materials and methods: The study was conducted on a colon carcinoma tumor model in Balb/c mice. The colon carcinoma tumors were induced in the mice by subcutaneous injection. Twenty four hours after intraperitoneal injection of Zinc Phthalocyanine liposome as a sensitizer, at first ultrasound irradiation with a known frequency and intensity was performed followed by illumination of the tumor area. Evaluation of the treatment efficacy was done using daily measurement of the tumors and calculation of their relative volumes. Also, all control groups were considered to confirm the effect of each therapeutic option in the study. Results: In the first ten days post treatment, the relative volumes of all groups decreased significantly in comparison with the main control group, but the best response was observed in the photodynamic or sonodynamic therapy groups. The longest doubling time of tumor size was related to groups under photodynamic, sonodynamic and main therapies, and the shortest belonged to the control group. Discussion and conclusion: Zinc phthalocyanine liposome is both a photosensitizer and sonsensitizer. Photodynamic and sonodynamic therapies can be efficient in retarding tumor growth rate. In this study, combination of the two methods did not cause improved therapeutic outcomes. It is predicted that this result is related to the choice of therapeutic agents and could be optimized in future.

The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)-mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U-118 MG cells was detected by flow cytometry (FCM). A 630-nm semiconductor laser and 1-MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit-8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U-118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U-118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS-mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl-xL, increased cleaved -caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl-xL and in the levels of cleaved-caspase 3 were partly reversed by N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS-mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.

The photo-physicochemical properties and in vitro sonophotodynamic therapy activity of Di-axially substituted silicon phthalocyanines on PC3 prostate cancer cell line

Efficacy of Methylene Blue and Aliminium Phthalocyanine Mediated Sonophotodynamic Therapy on Prostate Cancer Cell Lines

Comparison of sonodynamic, photodynamic and sonophotodynamic therapy activity of fluorinated pyridine substituted silicon phthalocyanines on PC3 prostate cancer cell line

Comparing the efficacy of photodynamic and sonodynamic therapy in non-melanoma and melanoma skin cancer

Water-soluble graphene quantum dots (GQDs) have recently exhibited considerable potential for diverse biomedical applications owing to their exceptional optical and chemical properties. However, the pronounced heterogeneity in the composition, size, and morphology of GQDs poses challenges for a comprehensive understanding of the intricate correlation between their structural attributes and functional properties. This variability also introduces complexities in scaling the production processes and addressing safety considerations. Light and sound have firmly established their role in clinical applications as pivotal energy sources for minimally invasive therapeutic interventions. Given the limited penetration depth of light, photodynamic therapy (PDT) predominantly targets superficial conditions such as dermatological disorders, head and neck malignancies, ocular ailments, and early-stage esophageal cancer. Conversely, ultrasound-based sonodynamic therapy (SDT) capitalizes on its superior ability to propagate and focus ultrasound within biological tissues, enabling a diverse range of therapeutic applications, including the management of gliomas, breast cancer, hematological tumors, and modulation of the blood-brain barrier (BBB). Considering the advancements in theranostic and precision therapies, reevaluating these conventional energy sources and their associated sensitizers is imperative. This review introduces three prevalent treatment modalities that harness light and sound stimuli: PDT, SDT, and a synergistic approach that integrates PDT and SDT. This study delineated the therapeutic dynamics and contemporary designs of sensitizers tailored to these modalities. By exploring the historical context of the field and elucidating the latest design strategies, this review underscores the pivotal role of GQDs in propelling the evolution of PDT and SDT. This aspires to stimulate researchers to develop "multimodal" therapies integrating both light and sound stimuli.

Glioblastoma multiforme (GBM), the most aggressive form of brain cancer, poses substantial challenges to effective treatment due to its complex and infiltrative nature, making it difficult to manage. Photodynamic therapy (PDT) and sonodynamic therapy (SDT), have emerged as promising individual treatment options against GBM due to their least-invasive approach. However, both PDT and SDT have drawbacks that require careful consideration. A combination therapy using light and sound waves has gained attention, offering new avenues to overcome challenges from individual therapies. Sono-photodynamic therapy (SPDT) has been used against various tumours. Researchers are considering SPDT as a favourable alternative to the conventional therapies for GBM. SPDT offers complementary mechanisms of action, including the production of ROS, disruption of cellular structures, and induction of apoptosis, leading to enhanced tumour cell death. This review gives an insight about PDT/SDT and their limitations in GBM treatment and the need for combination therapy. We try to unveil the process of SPDT and explore the mechanism behind improved SPDT-meditated cell death in GBM cells by focusing on the ROS-mediated cell response occurring as a result of SPDT and discussing current modifications in the existing sensitisers for their optimal use in SPDT for GBM therapy.

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.

This article presents the construction of a multimodality platform that can be used for efficient destruction of brain tumor by a combination of photodynamic and sonodynamic therapy. For in vivo studies, U87 patient-derived xenograft tumors were implanted subcutaneously in SCID mice. For the first time, it has been shown that the cell-death mechanism by both treatment modalities follows two different pathways. For example, exposing the U87 cells after 24 h incubation with HPPH [3-(1′-hexyloxy)ethyl-3-devinyl-pyropheophorbide-a) by ultrasound participate in an electron-transfer process with the surrounding biological substrates to form radicals and radical ions (Type I reaction); whereas in photodynamic therapy, the tumor destruction is mainly caused by highly reactive singlet oxygen (Type II reaction). The combination of photodynamic therapy and sonodynamic therapy both in vitro and in vivo have shown an improved cell kill/tumor response, that could be attributed to an additive and/or synergetic effect(s). Our results also indicate that the delivery of the HPPH to tumors can further be enhanced by using cationic polyacrylamide nanoparticles as a delivery vehicle. Exposing the nano-formulation with ultrasound also triggered the release of photosensitizer. The combination of photodynamic therapy and sonodynamic therapy strongly affects tumor vasculature as determined by dynamic contrast enhanced imaging using HSA-Gd(III)DTPA.

Iridium and rhenium complexes in photodynamic and sonodynamic therapy: mechanistic insights and therapeutic potential.

Sonodynamic and photodynamic therapy, activated indocyanine green, and indocyanine green-loaded chitosan nanoparticle on resin tag length and shear bond strength to caries-affected dentin using two-step etch and rinse resin adhesive.

Objective(s) Although photodynamic therapy is considered as a noninvasive method, most photosensitizers are susceptible to ultrasound. Therefore, it is expected that the combination of two activation methods might have a synergistic effect. This probable effect has been investigated in this study. Materials and Methods This study was conducted on colon carcinoma tumor in Balb/c mice. The tumors were induced by subcutaneous injection of CT26 cells. Ultrasound and light irradiations were performed on tumors 24 hr after injection of liposomal Zn (II)-phthalocyanine. The treatment efficacy was evaluated using daily measurement of the tumor dimensions. Results Ten days post treatment, relative tumor volumes of all groups were significantly reduced in comparison with the main control group. The best response was observed when one of the two treatment methods had been applied. The longest doubling time of tumor was related to the treatment group namely photodynamic, sonodynamic and combination technique, while the shortest belonged to the control group. Conclusion This study showed that liposomal Zn phthalocyanine is both photosensitizer and sonosensitizer. Photodynamic and sonodynamic therapies can be efficient in retarding tumor growth rate. In this study, the combination of two methods didn’t show any improvement in therapeutic outcomes. It is predicted that latest results are related to the treatments sequence and could be optimized in the future.

118 Background: Sonodynamic therapy (SDT), a procedure related with photodynamic therapy, is a promising new modality for treating deep-seated cancer. Two new chlorophyll derived sono-photo-sensitizing agents, along with equipment for systemic SDT, have been developed by EEC Biotech and all approved by regulator for safety on human. Animal studies demonstrate that the sensitizers are specifically absorbed into tumor cells and SDT does inhibit growth of mouse S-180 sarcoma. An in vitro experiment with human breast cancer cell-line showed that SDT was strongly synergetic with chemotherapy. Using sono-photo-dynamic therapy (SPDT) as a supplementary or salvage treatment, we have got some positive results in advanced refractory breast cancers. Methods: Twelve patients were pathologically proven advanced breast carcinoma. Eleven had metastases in viscera including brain, and nine in bones. Ten had chemotherapy before, nine failed at least second lines of conventional chemotherapy. With SPDT, Patients took the sensitizers sublingually on days 1 and 2, red light and multiple ultrasound transducers irradiate tumor area and whole body on days 4 to 6. The treatment was repeated. Nine patients had concurrent chemo with range from moderate to ¼ conventional dosages selected to keep side effects at grade II or better. Results: The twelve patients achieved CR 3(25%), PR 6 (50%), MR 1, SD 2, with an overall response rate of 75%.Median overall survival exceeded 14.5 months. SPDT as sole therapy was effective in three cases. Four treated repeatly with SPDT also achieved positive result after tumor relapsed. One patient with brain metastases showed much reduced. The two SD were TNBC with inflammation-like metastases on the chest surface. The main SPDT side effects were easily reversible mild pain in tumor areas, tiredness and weakness.There was no skin sensitivity.SPDT/dose controlled chemo was well tolerated, even a terminally ill patient was treated safely and effectively. Conclusions: These preliminary data suggest that SPDT has almost no toxicity, and may dramatically enhance chemo efficacy in some refractory advanced breast cancer cases. SPDT has a good trend to be a new systemic, low toxicity tumor therapy and merit for further investigation.

Activated Ca ncer Ther apy ( ACT), al so know n a s Sonodyna mic Phot odynamic Ther apy ( SPDT) i s a nove l therapeutic modality that utilises a non-toxic photosensitive agent with reported ultrasound-activated properties. SPDT has previously demonstrated significant tumour cell inhibition in animal studies. There has been much research into the effi- cacy of phot odynamic therapy and development in understanding of the underlying mechanism of tumour cytotoxicity. Synergistic ultrasound activation represents a promising development to activated sensitiser therapy, as photo-activation is limited by access and penetrance issues. Ultrasound has been demonstrated to activate a number of sono-sensitive agents allowing the possibility of non-invasive targeted treatment o f deeper tumour sites than is currently achievable with pho- todynamic therapy. Thi s case se ries of 115 pa tients w ith a v ariety of ca ncer di agnoses reports on experiences of this treatment over a 4 year period using sublingual administration of a new dual activation agent, Sonnelux-1, followed by a protocol of LED light and low-intensity ultrasound exposure. Initial clinical observation suggests SPDT is worthy of fur- ther investigation a s an ef fective and w ell to lerated t reatment fo r a w ide v ariety o f p rimary an d m etastatic tumours, in- cluding those refractory to chemotherapy. Key Wo rds: Sonodynamic therapy, photodynamic therapy, activated cancer therapy, u ltrasound activated therapy, m etastatic cancer, sonnelux-1, dove clinic, sonnemed.