Anti-metastatic and pro-apoptotic effects elicited by combination photodynamic therapy with sonodynamic therapy on breast cancer both in vitro and in vivo

Sono-Photodynamic therapy (SPDT), a new modality for cancer treatment, is aimed at enhancing anticancer effects by the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we investigated the antitumor effect and possible mechanisms of Chlorin e6 (Ce6) mediated SPDT (Ce6-SPDT) on breast cancer both in vitro and in vivo. MTT assay revealed that the combined therapy markedly enhanced cell viability loss of breast cancer cell lines (MDA-MB-231, MCF-7 and 4T1) compared with SDT and PDT alone. Propidium iodide/hoechst33342 double staining reflected that 4T1 cells with apoptotic morphological characteristics were significantly increased in groups given combined therapy. Besides, the combined therapy caused obvious mitochondrial membrane potential (MMP) loss at early 1 h post SPDT treatment. The generation of intracellular reactive oxygen species (ROS) detected by flow cytometry was greatly increased in 4T1 cells treated with the combination therapy, and the loss of cell viability and MMP could be effectively rescued by pre-treatment with the ROS scavenger N-acetylcysteine (NAC). Further, Ce6-SPDT markedly inhibited the tumor growth (volume and weight) and lung metastasis in 4T1 tumor-bearing mice, but had no effect on the body weight. Hematoxylin and eosin staining revealed obvious tissue destruction with large spaces in the Ce6-SPDT groups, and TUNEL staining indicated tumor cell apoptosis after treatment. Immunohistochemistry analysis showed that the expression level of VEGF and MMP were significantly decreased in the combined groups. These results indicated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, loss of MMP and generation of ROS might be involved. In addition, Ce6-mediated SPDT significantly inhibited tumor growth and metastasis in mouse breast cancer 4T1 xenograft model, in which MMP-9 and VEGF may play a crucial role.     

Bleomycin enhances the efficacy of sonodynamic therapy using aluminum phthalocyanine disulfonate

Sonodynamic therapy (SDT), or ultrasound combined with sonosensitization, is a promising approach because it is noninvasive and penetrates deeper than light does in photodynamic therapy. We examined whether bleomycin (BLM) could improve the efficacy of SDT. We performed an in vitro study using Colon-26 cells, which are derived from mouse colon cancer. SDT with BLM was significantly more cytotoxic than SDT alone both in vitro and in vivo. We also observed an ultrasound intensity-dependent cytotoxic effect of SDT with BLM. These findings suggest that SDT with BLM might provide a novel noninvasive treatment for deep-seated tumors.     

Nanosonosensitization by Using Copper–Cysteamine Nanoparticles Augmented Sonodynamic Cancer Treatment

Sonodynamic therapy (SDT), as a newly emerging and promising modality for cancer treatment, has been extensively investigated but with limited therapeutic outcome because of the absence of highly efficient sonosensitizer. Copper–cysteamine (Cu–Cy), as a new sensitizer, has been reported for oxidative therapy which can be activated with light, X‐ray, or microwave. Herein, for the first time, Cu–Cy nanoparticles are reported as new sonosensitizers for SDT on breast cancer treatment. Upon exposure of Cu–Cy nanoparticles to ultrasound, a large quantity of reactive oxygen species (ROS) are generated for cancer cell destruction with a high SDT efficiency to induce cell apoptosis and necrosis as observed in vitro. In vivo animal studies show a significant inhibition of tumor growth for the xenografts of 4T1 cancer cells with the combination of 0.75 mg kg⁻¹ Cu–Cy and ultrasound. Overall, the preliminary results show that Cu–Cy nanoparticles can significantly augment the levels of ROS induced by ultrasound, demonstrating Cu–Cy is a new kind of efficient sonosensitzers for SDT applications. Such therapeutic platform by integrating a noninvasive, highly safe, deep‐penetration ultrasound modality. and quickly developed versatile nanosensitizers for tumor eradication will facilitate SDT future clinical translation.     

The tumor affinity of chlorin e6 and its sonodynamic effects on non-small cell lung cancer

ObjectiveSonodynamic therapy (SDT) is a promising new approach for cancer therapy. The aim of this study was to investigate the tumor affinity of chlorin e6, a photosensitizer, and its sonodynamic effects on NSCLC.MethodsHuman lung adenocarcinoma cells SPCA-1 and mice bearing SPCA-1 tumor xenograft were exposed to ultrasound in the presence or absence of chlorin e6. Chlorin e6 distribution was detected by laser scan confocal microscope. Cell apoptosis and necrosis were studied by flow cytometry analysis. Tumor size and weight were measured after different treatments.ResultsThe concentration of chlorin e6 in tumor tissue was remarkably higher than that in normal muscle near tumor, and the difference was greatest at 18 h (the fluorescence intensity was 5.38-fold higher in tumor than in muscle, P < 0.05). In vivo, ultrasound (0.4–1.6 W/cm²) or chlorin e6 (10–40 mg/kg) alone had no remarkable anti-tumor effects, but the combination of ultrasound (1.6 W/cm²) with chlorin e6 (SDT) hampered tumor growth significantly (P < 0.05). Intraperitoneal injection of 40 mg/kg chlorin e6 exerted no notable side effect on blood, liver and kidney function. Flow cytometry analysis showed that chlorin e6-mediated sonodynamic effect was mainly through the induction of cell necrosis.ConclusionChlorin e6 is a promising sonosensitizer and chlorin e6-mediated SDT may provide a new approach for NSCLC therapy.     

Preparation of sonoactivated TiO2-DVDMS nanocomposite for enhanced antibacterial activity

Titanium dioxide (TiO₂) nanoparticle has good photo-/sono-catalytic features, the reunion of this particle in solution-phase generally limits the extensive biomedical application. In the present study, the aggregation of TiO₂ nanoparticles was alleviated by facile fabrication under different pH conditions. A novel TiO₂ nanocomposite was further synthesized by properly conjugation with trace amount of DVDMS sensitizer (named DFT). The characterization, sonoactivity, as well as the antibacterial efficiency were specially evaluated. The results showed that the sonochemical activity of DFT was greatly improved as compared with the simple surface modification of TiO₂ (F-TiO₂) and free DVDMS, regarding to the hydroxyl radicals and singlet oxygen yields using the same ultrasound exposure. Moreover, ultrasonic stimulation of DFT exhibited excellent bacterial eradication, with up to 92.41% of killing efficiency in S. aureus. The flow cytometry analysis indicated an increased intracellular ROS and membrane disturbance by combination of DFT and ultrasound. The findings suggest that the proper fabrication and DVDMS incorporation greatly improved the sonocatalytic process of TiO₂, and the ultrasound based biomedical applications of DFT deserve future deep investigation.     

Membrane fluidity altering and enzyme inactivating in sarcoma 180 cells post the exposure to sonoactivated hematoporphyrin in vitro

Sonodynamic therapy (SDT) is a novel tumor therapy method. We investigated membrane fluidity, activity of the enzymes and membrane morphology in vitro post hematoporphyrin-SDT treatment. Furthermore, the potential mechanisms behind the changes in membrane fluidity and enzymic activity were discussed. Tumor cells were exposed to ultrasound at 1.75 MHz for up to 3 min in the presence and absence of hematoporphyrin. Fluorescence polarization, contents of Malonaldehyde, and levels of free fatty acid were assessed. Activity of enzymes was checked by the plumbic nitrate detection method. For the morphologic study, a scanning electron microscope was used to observe the cellular surface. Ultrasonically induced cell damage increased in the presence of HPD (from 15% to 24%). Compared with ultrasound treatment alone, the fluidity decreased from 5.037 to 3.908, malonaldehyde content and free fatty acid level increased from 0.743 nmol/mL to 0.979 nmol/mL and from 237.180 μmol/L to 730.769 μmol/L, respectively, post ultrasound combined with HPD treatment. Inactivity of adenylate cyclase and guanylate cyclase and significant deformation of the cellular surface were also observed post SDT treatment. Our results suggested that alterations in membrane modality and lipid composition played important roles in SDT-mediated inhibition of tumor growth, even inducing tumor cell death, which might be attributed to a sono-chemical activation mechanism.     

Current status and future perspectives of sonodynamic therapy in glioma treatment

Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies. The ultrasound waves can penetrate deep tissues and reversibly open the blood-brain barrier to enhance drug delivery to the brain. Thus, sonodynamic therapy has a promising potential in glioma treatment. In this review, we summarize the studies that have confirmed the pre-clinical efficacy of sonodynamic therapy for glioma treatment, and discuss the future directions for this emerging treatment.     

The effects of Ce6-mediated sono-photodynamic therapy on cell migration,apoptosis and autophagy in mouse mammary 4T1 cell line

Purpose

Sono-Photodynamic therapy (SPDT) is an alternative therapy which claims to enhance the anti-cancer effects by combining sonodynamic therapy (SDT) with photodynamic therapy (PDT). In the present study, we investigated the effects of chlorin e6 (Ce6) mediated SPDT on migration, apoptosis and autophagy in mouse mammary 4T1 cancer cells, and its underlying mechanisms.

Materials

Cell migration was determined by wound healing assay. Apoptosis was analyzed using annexin V-PE/7-ADD staining as well as Hoechst 33342 staining. Changes of mitochondria membrane potential (MMP) was evaluated by flow cytometry. Formation of acidic vesicular organelles (AVOs) during autophagy was observed with fluorescence microscope by MDC staining. Immunofluorescence assays were performed to detect the co-localization of LC3 and Lamp2. Western blotting was employed to analyze the activity of the apoptosis related proteins Caspase-3, PARP, Bax and Bcl-2, as well as the autophagy associated processing of LC3-I to LC3-II and Beclin-1 expression.

Results

Ce6 mediated SPDT further enhanced cell migration inhibition, significantly triggered cell apoptosis, nuclear condensation and MMP drop. Cleaved Caspase-3 and PARP increased dramatically after Ce6-SPDT, accompanied by decreased Bcl-2 expression, while the expression of Bax remained stable. Additionally, AVOs formation, co-localization of LC3 and Lamp2 occurred following Ce6-SPDT and simultaneously accompanied by LC3-II processing and increased Beclin-1 expression.

Conclusions

Ce6-SPDT could enhance cell migration inhibition, and induce mitochondria-dependent apoptosis as well as autophagy in 4T1 cells.     

Sonodynamic action of pyropheophorbide-a methyl ester induces mitochondrial damage in liver cancer cells

Sonodynamic therapy with pyropheophorbide-a methyl ester (MPPa) presents a promising aspect in treating liver cancer. The present study aims to investigate the mitochondrial damage of liver cancer cells induced by MPPa-mediated sonodynamic action. Mouse hepatoma cell line H₂₂ cells were incubated with MPPa (2 μM) for 20 h and then exposed to ultrasound with an intensity of 0.97 W/cm² for 8 s. Cytotoxicity was investigated 24 h after sonodynamic action using MTT assay and light microscopy. Mitochondrial membrane potential (ΔΨm) was analyzed using flow cytometry with rhodamine 123 staining and ultrastructural changes were observed using transmission electron microscopy (TEM).The cytotoxicity of MPPa-mediated SDT on H₂₂ cell line was 73.00 ± 3.42%, greater than ultrasound treatment alone (28.12 ± 5.19%) significantly while MPPa treatment alone had no significant effect on H₂₂ cells. Moreover, after MPPa-mediated SDT cancer cells showed swollen mitochondria under TEM and a significant collapse of mitochondrial membrane potential. Our findings demonstrated that MPPa-mediated SDT could remarkably induce cell death of H₂₂ cells, and highlighted that mitochondrial damage might be an important cause of cell death induced by MPPa-mediated SDT.     

ROS-generating alginate-coated gold nanorods as biocompatible nanosonosensitisers for effective sonodynamic therapy of cancer

Sonodynamic therapy (SDT) emerges as a promising non-invasive alternative for eradicating malignant tumours. However, its therapeutic efficacy remains limited due to the lack of sonosensitisers with high potency and biosafety. Previously, gold nanorods (AuNRs) have been extensively studied for their applications in photodynamic or photothermal cancer therapy, but their sonosensitising properties are largely unexplored. Here, we reported the applicability of alginate-coated AuNRs (AuNRs^ALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRs^ALG were found stable under ultrasound irradiation (1.0 W/cm², 5 min) and maintained structural integrity for 3 cycles of irradiation. The exposure of the AuNRs^ALG to ultrasound irradiation (1.0 W/cm², 5 min) was shown to enhance the cavitation effect significantly and generate a 3 to 8-fold higher amount of singlet oxygen (¹O₂) than other reported commercial titanium dioxide nanosonosensitisers. AuNRs^ALG exerted dose-dependent sonotoxicity on human MDA-MB-231 breast cancer cells in vitro, with ∼ 81% cancer cell killing efficacy at a sub-nanomolar level (IC₅₀ was 0.68 nM) predominantly through apoptosis. The protein expression analysis showed significant DNA damage and downregulation of anti-apoptotic Bcl-2, suggesting AuNRs^ALG induced cell death through the mitochondrial pathway. The addition of mannitol, a reactive oxygen species (ROS) scavenger, inhibited cancer-killing effect of AuNRs^ALG-mediated SDT, further verifying that the sonotoxicity of AuNRs^ALG is driven by the production of ROS. Overall, these results highlight the potential application of AuNRs^ALG as an effective nanosonosensitising agent in clinical settings.     

Sonodynamically induced anti-tumor effect with protoporphyrin IX on hepatoma-22 solid tumor

Objective

The purpose of this study was to evaluate sonodynamically induced anti-tumor effect of protoporphyrin IX (PPIX) in mice bearing hepatoma-22 (H-22) solid tumors, and the possible in vivo cell damage mechanism was also investigated.

Methods

The pharmacokinetics of PPIX was analyzed in plasma, skin, muscle and tumor of H-22 bearing mice. Tumors were irradiated with ultrasound (1.43 MHz, I_SATA 3 W/cm², 3 min) for three times at 8, 12 and 24 h after 5.0 mg/kg PPIX administration, respectively. The anti-tumor effects of sonodynamic therapy (SDT) were estimated by the tumor inhibition ratio (volume and weight). The bio-effects of SDT were evaluated by hematoxylin and eosin (H&E) staining, transmission electron microscope (TEM) observation, lipid peroxidation (LPO) measurement and anti-oxidative enzymes (glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD)) assay.

Results

A significant anti-tumor effect was obtained by PPIX-mediated sonodynamic therapy (PPIX-SDT). At the fifteenth day after PPIX-SDT, the tumor growth and tumor weight inhibition ratios were 53.84% and 45.86%, respectively. In addition, the structure of tumor tissues and the anti-oxidative enzymes were obviously destroyed after SDT treatment.

Conclusions

A biochemical mechanism was involved in PPIX-SDT in vivo, and the free radicals produced by the synergistic treatment destroying the anti-oxidative system of tumor cells in vivo may play an important role in this action. Also, the thermal effect could not be excluded in inducing damage of cellular structures, like membrane disruption and chromatin condensation under current evaluation in this paper.     

Enhanced sonodynamic therapy by carbon dots-shelled microbubbles with focused ultrasound

Sonodynamic therapy involving the non-invasive and local generation of lethal reactive oxygen species (ROS) via ultrasound (US) with sonosensitizers has been proposed as an emerging tumor therapy strategy. However, such therapy is usually associated with inertial cavitation and unnecessary damage to healthy tissue because current sonosensitizers have insufficient sensitivity to US. Here, we report the use of a new proposed sonosensitizer, carbon dots (C-dots), to assemble microbubbles with a gas core (C-dots MBs). As the C-dots were directly integrated into the MB shell, they could effectively absorb the energy of inertial cavitation and transfer it to ROS. Our results revealed the appearance of ¹O₂, •OH, and H₂O₂ after US irradiation of C-dots MBs. In in vitro experiments, treatment with C-dots MBs plus US induced lipid peroxidation, elevation of intracellular ROS, and apoptosis in 32.5%, 45.3%, and 50.1% of cells respectively. In an animal solid tumor model, treatment with C-dots MBs plus US resulted in a 3-fold and 2.5-fold increase in the proportion of ROS-damaged cells and apoptotic cells, respectively, compared to C-dots MBs alone. These results will pave the way for the design of novel multifunctional sonosensitizers for SDT tumor therapy.     

Sonodynamic therapy combined with novel anti-cancer agents,sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro

The presence of ultrasound-induced cavitation in sonodynamic therapy (SDT) treatments has previously enhanced the activity and delivery of certain sonosensitisers in biological systems. The purpose of this work was to investigate the potential for two novel anti-cancer agents from natural derivatives, sanguinarine and ginger root extract (GRE), as sonosensitisers in an SDT treatment with in vitro PANC-1 cells. Both anti-cancer compounds had a dose-dependent cytotoxicity in the presence of PANC-1 cells. A range of six discreet ultrasound power-frequency configurations were tested and it was found that the cell death caused directly by ultrasound was likely due to the sonomechanical effects of cavitation. Combined treatment used dosages of 100 μM sanguinarine or 1 mM of GRE with 15 s sonication at 500 kHz and 10 W. The sanguinarine-SDT and GRE-SDT treatments showed a 6% and 17% synergistic increase in observed cell death, respectively. Therefore both sanguinarine and GRE were found to be effective sonosensitisers and warrant further development for SDT, with a view to maximising the magnitude of synergistic increase in toxicity.     

Magnetic nanoemulsions as drug delivery system for Foscan: Skin permeation and retention in vitro assays for topical application in photodynamic therapy (PDT) of skin cancer

In this work, we performed the synthesis and in vitro characterization of a new class of drug delivery system (DDS) denominated magnetic nanoemulsion (MNE). The association of colloidal nanoparticles with biocompatible magnetic fluids results in a new DDS for application in photodynamic therapy (PDT) and magnetic hyperthermia treatment. It works in a synergic manner with an expected enhancement in tumor damage after minimum drug doses, based on heat dissipation and/or light photosensitization. For this purpose, we investigated the permeation and retention in vitro model using Foscan^® as a photosensitizer incorporated in MNE using a Franz diffusion cell and a biological skin model in biomimetic conditions.     

Acute effects of sono-activated photocatalytic titanium dioxide nanoparticles on oral squamous cell carcinoma

Sonodynamic therapy (SDT) is a new treatment modality using ultrasound to activate certain chemical sensitizers for cancer therapy. In this study, effects of high intensity focused ultrasound (HIFU) combined with photocatalytic titanium dioxide (TiO₂) nanoparticles on human oral squamous cell line HSC-2 were investigated. Viability of HSC-2 cells after 0, 0.1, 1, or 3 s of HIFU irradiation with 20, 32, 55 and 73 W cm⁻² intensities in the presence or absence of TiO₂ was measured immediately after the exposures in vitro. Immediate effects of HIFU (3 s, 73 W cm⁻²) combined with TiO₂ on solid tumors were also examined by histological study. Cytotoxic effect of HIFU + TiO₂ in vitro was significantly higher than that of TiO₂ or HIFU alone with the tendency to increase for higher HIFU intensity, duration, and TiO₂ concentration in the suspension. In vivo results showed significant necrosis and tissue damage in HIFU and HIFU + TiO₂ treated samples. However, penetration of TiO₂ nanoparticles into the cell cytoplasm was only observed in HIFU + TiO₂ treated tissues. In this study, our findings provide a rational basis for the development of an effective HIFU based sonodynamic activation method. This approach offers an attractive non-invasive therapy technique for oral cancer in future.     

Oxygen-carrying biomimetic nanoplatform for sonodynamic killing of bacteria and treatment of infection diseases

Among various novel antimicrobial therapies, sonodynamic therapy (SDT) exhibits its advantages for the treatment of bacterial infections due to its high penetration depth and low side effects. In this study, a new nanosonosensitizer (HFH@ZIF-8) that loads sonosensitizer hematoporphyrin monomethyl ether (HMME) into zeolitic imidazolate framework-8 (ZIF-8), was constructed for killing multidrug-resistant (MDR) bacteria and treatment of in vivo infection diseases by SDT. In particular, the developed HFH@ZIF-8 exhibited enhanced water-solubility, good biocompatibility, and improved disease-targeting capability for delivering and releasing HMME and ablating the infected lesion. More importantly, the presence of oxygen-carrying hemoglobin for HFH@ZIF-8 can offer sufficient oxygen consumption by SDT, augmenting the efficacy of SDT by improving ROS generating efficiency against deep tissue multidrug-resistant bacterial infection. Therefore, this study paves a new avenue for treating infection disease, particularly for antibiotic resistant bacterial infection.     

In vivo relaxation time measurements on a murine tumor model—Prolongation of T1 after photodynamic therapy

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T₁ and T₂) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed using the untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T₁s of water protons were observed after PDT treatment. In all experiments, ³¹P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T₁s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T₂ values after PDT treatment.     

Ultrasound exposure in the presence of hematoporphyrin induced loss of membrane integral proteins and inactivity of cell proliferation associated enzymes in sarcoma 180 cells in vitro

Ultrasonically induced effects of hematoporphyrin (HPD) on cell damage and membrane protein alteration of S180 isolated tumor cells in vitro were investigated, and the potential mechanisms of sonodynamic therapy (SDT) inhibiting tumor growth were discussed. Tumor cells suspended in air-saturated PBS (pH 7.2) were exposed to ultrasound at 1.8 MHz for up to 180 s in the presence and absence of HPD. The viability of cells was determined by a trypan blue exclusion test. To estimate the damage effects of SDT on plasma membrane of tumor cells primarily, membrane integral proteins (EGFR, Ras, Fas, FasL) and cell proliferation associated enzymes (adenylate cyclase and guanylate cyclase) were checked with immunochemical methods. The results indicated that the intensity threshold for ultrasonically induced cell damage at 1.8 MHz was 3 W/cm². At this condition, the expression of the integral proteins was obviously inhibited and the activity of the enzymes was decreased post ultrasound treatment in the presence of 20 μg/ml HPD. Loss of the membrane proteins and inactivity of AC and GC post SDT was time-dependent. This paper reveals SDT can cause the loss of tumor cell membrane integral proteins and inactivity of the enzymes associated with cell proliferation which might be attributed to a sonochemical activation mechanism. The mechanisms by that tumor growth is inhibited by SDT can be understood as that the growth signaling pathway is partially interdicted and the resistance of tumor cells to the specifically activated immune cells is weakened.     

Novel S-Gal analogs as H MRI reporters for in vivo detection of β-galactosidase

The quantitative assessment of gene expression and related enzyme activity in vivo could be important for the characterization of gene altering diseases and therapy. The development of imaging techniques, based on specific reporter molecules may enable routine non-invasive assessment of enzyme activity and gene expression in vivo. We recently reported the use of commercially available S-Gal^® as a β-galactosidase reporter for ¹H MRI, and the synthesis of several S-Gal^® analogs with enhanced response to β-galactosidase activity. We have now compared these analogs in vitro and have identified the optimal analog, C3-GD, based on strong T₁ and T₂ response to enzyme presence (ΔR₁ and ΔR₂ ~ 1.8 times S-Gal^®). Moreover, application is demonstrated in vivo in human breast tumor xenografts. MRI studies in MCF7-lacZ tumors implanted subcutaneously in athymic nude mice (n = 6), showed significant reduction in T₁ and T₂ values (each ~ 13%) 2 h after intra-tumoral injection of C3-GD, whereas the MCF7 (wild type) tumors showed slight increase. Thus, C3-GD successfully detects β-galactosidase activity in vivo and shows promise as a lacZ gene ¹H MR reporter molecule.     

Porous Lanthanum-Doped Manganese Oxide Nanoparticles for Enhanced Sonodynamic Cancer Therapy

Metal oxides hold great promise as robust sonosensitizers for sonodynamic therapy (SDT). However, they usually suffer from limited production yield of reactive oxygen species (ROS) due to the fast recombination of ultrasound-triggered electrons and holes. Herein, porous lanthanum (La)-doped MnO₂ (LMO) nanoparticles are firstly developed as promising sonosensitizers in SDT. The strategic introduction of La dopants greatly promotes the separation efficiency of ultrasound-triggered electrons and holes of MnO₂, endowing them with significantly improved ROS yield. Consequently, the LMO with polyethylene glycol decoration exhibits good SDT activity toward breast cancer cells. This work highlights the doping strategy for the development of enhanced ROS production of metal oxide sonosensitizers for SDT.