Ultrasound targeted microbubble destruction combined with Fe-MOF based bio-/enzyme-mimics nanoparticles for treating of cancer.
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ABSTRACT:
SUBMITTER: Xiang X
PROVIDER: S-EPMC8011114 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Melanoma is one of the most aggressive types of cancer, and its incidence has increased rapidly in the past few decades. In this study, we investigated a novel treatment approach, the use of low-intensity ultrasound (2.3 W/cm2 at 1?MHz)-mediated Optison microbubble (MB) destruction (UMMD) to treat melanoma in a flank tumor model. The effect of UMMD was first evaluated in the melanoma cell line B16 F10 (B16) in vitro and then in mice inoculated with B16 cells. MB+B16 cells were exposed to US in vitro, resulting in significant cell death proportional to duty cycle (R2?=?0.74): approximately 30%, 50%, 80% and 80% cell death at 10%, 30%, 50% and 100% DC respectively. Direct implantation of tumors with MBs, followed by sonication, resulted in retarded tumor growth and improved survival (p?=?0.0106). Immunohistochemical analyses confirmed the significant changes in expression of the cell proliferation marker Ki67 (p?=?0.037) and a microtubule-associated protein 2 (p?=?0.048) after US?+?MB treatment. These results suggest that UMMD could be used as a possible treatment approach in isolated melanoma and has the potential to translate to clinical trials.
| S-EPMC5826859 | biostudies-literature
Project description:ObjectiveTo investigate the efficacy and mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with radiotherapy (XRT) on glioblastoma.MethodsThe enhanced radiosensitization by UTMD was assessed through colony formation and cell apoptosis in Human glioblastoma cells (U87MG). Subcutaneous transplantation tumors in 24 nude mice implanted with U87MG cells were randomly assigned to 4 different treatment groups (Control, UTMD, XRT, and UTMD + XRT) based on tumor sizes (100-300 mm3). Tumor growth was observed for 10 days after treatment, and then histopathology stains (HE, CD34, and γH2AX) were applied to the tumor samples. A TUNEL staining experiment was applied to detect the apoptosis rate of mice tumor samples. Meanwhile, tissue proteins were extracted from animal specimens, and the expressions of dsDNA break repair-related proteins from animal specimens were examined by the western blot.ResultsWhen the radiotherapy dose was 4 Gy, the colony formation rate of U87MG cells in the UTMD + XRT group was 32 ± 8%, lower than the XRT group (54 ± 14%, p < 0.01). The early apoptotic rate of the UTMD + XRT group was 21.1 ± 3% at 48 h, higher than that of the XRT group (15.2 ± 4%). The tumor growth curve indicated that the tumor growth was inhibited in the UTMD + XRT group compared with other groups during 10 days of observation. In TUNEL experiment, the apoptotic cells of the UTMD + XRT group were higher than that of the XRT group (p < 0.05). The UTMD + XRT group had the lowest MVD value, but was not significantly different from other groups (p > 0.05). In addition, γH2AX increased due to the addition of UTMD to radiotherapy compared to XRT in immunohistochemistry (p < 0.05).ConclusionsOur study clearly demonstrated the enhanced destructive effect of UTMD combined with 4 Gy radiotherapy on glioblastoma. This could be partly achieved by the increased ability of DNA damage of tumor cells.
| S-EPMC8021517 | biostudies-literature
Project description:Low-intensity ultrasound-microbubble (LIUS-MB) treatment is a promising antivascular therapy for tumors. We sought to determine whether LIUS-MB treatment with an appropriate ultrasound pressure could achieve substantial and persistent cessation of tumor perfusion without having significant effects on normal tissue. Further, we investigated the mechanisms underlying this treatment. Murine S-180 sarcomas, thigh muscles, and skin tissue from 60 tumor-bearing mice were subjected to sham therapy, an ultrasound application combined with microbubbles in four different ultrasound pressures (0.5, 1.5, 3.0, 5.0 MPa), or ultrasound at 5.0 MPa alone. Subsequently, contrast-enhanced ultrasonic imaging and histological studies were performed. Tumor microvessels, tumor cell necrosis, apoptosis, tumor growth, and survival were evaluated in 85 mice after treatment with the selected ultrasound pressure. We found that twenty-four hours after LIUS-MB treatment at 3.0 MPa, blood perfusion and microvessel density of the tumor had substantially decreased by 84?±?8% and 84%, respectively (p?<?0.01). Similar reductions were not observed in the muscle or skin. Additionally, an extreme reduction in the number of immature vessels was observed in the tumor (reduced by 90%, p?<?0.01), while the decrease in mature vessels was not significant. Further, LIUS-MB treatment at 3.0 MPa promoted tumor cell necrosis and apoptosis, delayed tumor growth, and increased the survival rate of tumor-bearing mice (p?<?0.01). These findings indicate that LIUS-MB treatment with an appropriate ultrasound pressure could selectively and persistently reduce tumor perfusion by depleting the neovasculature. Therefore, LIUS-MB treatment offers great promise for clinical applications in antivascular therapy for solid tumors.
| S-EPMC5033025 | biostudies-literature
Project description:Ultrasound‑targeted microbubble destruction (UTMD) has recently been developed as a promising noninvasive tool for organ‑ and tissue‑specific gene or drug delivery. The aim of the present study was to explore the role of UTMD‑mediated Sirtuin 3 (SIRT3) overexpression in the malignant behaviors of human ovarian cancer (HOC) cells. Reverse transcription‑quantitative PCR was performed to detect SIRT3 mRNA expression levels in normal human ovarian epithelial cells and HOC cell lines; low SIRT3 expression was found in HOC cell lines, and the SKOV3 cell line was used in the following experiments. The SIRT3‑microbubble (MB) was prepared, and the effects of ultrasound‑treated SIRT3‑MB on biological processes of SKOV3 cells were determined. The proliferation, migration, invasion and apoptosis of SKOV3 cells were measured after SIRT3 upregulation by UTMD. Xenograft tumors in nude mice were induced to observe tumor growth in vivo. Upregulation of SIRT3 inhibited the malignant behaviors of SKOV3 cells, whereas UTMD‑mediated SIRT3 upregulation further inhibited proliferation, epithelial‑mesenchymal transition, invasion and migration, and induced apoptosis of SKOV3 cells, and it also inhibited tumor formation and growth in vivo. Moreover, the present study identified hypoxia inducible factor‑1α (HIF‑1α) as a target of SIRT3. The present study provided evidence that UTMD‑mediated overexpression of SIRT3 may suppress HOC progression through the inhibition of HIF‑1α.
| S-EPMC8377464 | biostudies-literature
Project description:We developed a method to spatially control gene expression following nonviral delivery of DNA. This method includes surface-modifying DNA nanocarriers with heparin to inhibit passive gene transfer in both the target and the off-target tissues and using ultrasound-targeted microbubble destruction (UTMD) to selectively activate heparin-inhibited gene transfer at the target site. We observed that the engraftment of heparin onto the surface of cationic liposomes reduced off-target gene expression in the liver, a major site of nanoplex accumulation, by more than 700-fold compared to the nonheparinized PEGylated liposomes. We further observed that tumor-directed UTMD increased gene transfer with heparin-modified nanoplexes by more than 10-fold. This method augmented tumor-to-liver selectivity of gene expression by 4000-fold compared to controls. We conclude that heparinization of DNA nanocarriers in conjunction with localized activation of gene transfer by UTMD may enable greater spatial control over genetic therapy.
| S-EPMC5240524 | biostudies-literature
Project description:Although gastric cancer therapy has been improved, more efficient treatment strategies still need to be developed. In the present study, a docetaxel (DOC)-loaded lipid microbubble (DLLD) was prepared and the effect of DLLD combined with ultrasound-triggered microbubble destruction (UTMD) on the growth of a gastric cancer cell line was investigated. The following four groups were included in the present study: Control, DOC, DLLD and DLLD plus UTMD. The determined entrapment efficiency of DLLD is 76±3.5%. The present study demonstrated that treatment with DLLD plus UTMD could significantly inhibit the growth of the cultured gastric cancer cell line BGC-823 via arresting the cell cycle in G2/M phase, inhibiting cell DNA synthesis, promoting cell apoptosis and disrupting mitochondrial membrane potential, as compared with treatment with DOC or DLLD alone. Furthermore, the expression of p53, p21 and Bax were identified to be significantly upregulated, while that of Bcl-2 was significantly downregulated in the DLLD plus UTMD group. Therefore, treatment with DLLD plus UTMD was more efficient in inhibiting cell proliferation and inducing cell apoptosis in the gastric cancer cell line, when compared with treatment with DOC or DLLD alone, suggesting that DLLD plus UTMD could serve as a promising strategy for the treatment of gastric cancer.
| S-EPMC6540049 | biostudies-literature
Project description:Cutaneous melanoma (CMM) is a skin tumor with a high degree of malignancy. BRAF resistance imposes great difficulty to the treatment of CMM, and partially contributes to the poor prognosis of CMM. YAP is involved in the growth and drug resistance of a variety of tumors, and mechanical signals may affect the activation of YAP1. As a novel ultrasound treatment technology, ultrasound-mediated microbubble destruction (UMMD) has been reported to have a killing effect on isolated CMM cells. In this study, the tumor tissue samples were collected from 64 CMM patients. We found that YAP1 mRNA expression was irrelevant to the clinicopathological characteristics and prognostic survival of the CMM patients. The drug-resistant cell line was constructed and subcutaneously implanted into nude mice, which were further separately treated with UMMD, ultrasound (US), and microbubbles (MB). The result showed that UMMD significantly inhibited the growth of tumor tissues. Ribosome imprinting sequencing (Ribo-seq) is a genetic technology for studying protein translation at genetic level. Ribo-seq, RNA-seq, and RT-qPCR were applied to detect YAP1 expression in CMM mouse tumor tissues. Ribo-seq data revealed that UMMD greatly up-regulated the expression of YAP1, interestingly, the up-regulated YAP1 was found to be negatively correlated with the weight of tumor tissues, while no significant change in YAP1 expression was detected by RNA-seq or RT-qPCR assay. These results indicated that UMMD could inhibit the tumor growth of drug-resistant CMM by affecting the translation efficiency of YAP1, providing a strong basis for the clinical treatment of UMMD in CMM.
| S-EPMC8117937 | biostudies-literature
Project description:The purpose of this study was to investigate whether ultrasound-targeted cationic microbubble destruction could effectively deliver endostatin-green fluorescent protein (ES-GFP) plasmids to human retinal vascular endothelial cells (HRECs).Cationic microbubbles (CMBs) were prepared and then compared with neutral microbubbles (NMBs) and liposomes. First, the two types of microbubbles were characterized in terms of size and zeta potential. The cell viability of the HRECs was measured using the 3-(4,5-dimthylthiazol-2-yl)-2,5 diphenyl-tetrazolium bromide (MTT) assay. The transcription and expression of endostatin, VEGF, Bcl-2, and Bcl-xl were measured via quantitative real-time PCR (qPCR) and western blotting, respectively.CMBs differed significantly from NMBs in terms of the zeta potential, but no differences in size were detected. Following ultrasound-targeted microbubble destruction (UTMD)-mediated gene therapy, the transcription and expression of endostatin were highest in the CMB group (p<0.05), while the transcription and expression of VEGF, Bcl-2, and Bcl-xl were lowest compared with the other groups. Moreover, the inhibition of HREC growth was enhanced following treatment with CMBs compared with NMBs or liposomes in vitro (p<0.01).This study demonstrated that ultrasound-mediated cationic microbubbles could enhance the transfection efficiency of ES-GFP, which had obvious impacts on the inhibition of the growth process of HRECs in vitro. These results suggest that the combination of UTMD and ES-GFP compounds might be a useful tool for gene therapy targeting retinal neovascularization.
| S-EPMC4548789 | biostudies-literature
Project description:Focused ultrasound combined with microbubble-mediated intranasal delivery (FUSIN) is a new brain drug delivery technique. FUSIN utilizes the nasal route for direct nose-to-brain drug administration, thereby bypassing the blood-brain barrier (BBB) and minimizing systemic exposure. It also uses FUS-induced microbubble cavitation to enhance transport of intranasally (IN) administered agents to the FUS-targeted brain location. Previous studies have provided proof-of-concept data showing the feasibility of FUSIN to deliver dextran and the brain-derived neurotrophic factor to the caudate putamen of mouse brains. The objective of this study was to evaluate the biodistribution of IN administered gold nanoclusters (AuNCs) and assess the feasibility and short-term safety of FUSIN for the delivery of AuNCs to the brainstem. Three experiments were performed. First, the whole-body biodistribution of IN administered 64Cu-alloyed AuNCs (64Cu-AuNCs) was assessed using in vivo positron emission tomography/computed tomography (PET/CT) and verified with ex vivo gamma counting. Control mice were intravenously (IV) injected with the 64Cu-AuNCs. Second, 64Cu-AuNCs and Texas red-labeled AuNCs (TR-AuNCs) were used separately to evaluate FUSIN delivery outcome in the brain. 64Cu-AuNCs or TR-AuNCs were administered to mice through the nasal route, followed by FUS sonication at the brainstem in the presence of systemically injected microbubbles. The spatial distribution of 64Cu-AuNCs and TR-AuNCs were examined by autoradiography and fluorescence microscopy of ex vivo brain slices, respectively. Third, histological analysis was performed to evaluate any potential histological damage to the nose and brain after FUSIN treatment. The experimental results revealed that IN administration induced significantly lower 64Cu-AuNCs accumulation in the blood, lungs, liver, spleen, kidney, and heart compared with IV injection. FUSIN enhanced the delivery of 64Cu-AuNCs and TR-AuNCs at the FUS-targeted brain region compared with IN delivery alone. No histological-level tissue damage was detected in the nose, trigeminal nerve, and brain. These results suggest that FUSIN is a promising technique for noninvasive, spatially targeted, and safe delivery of nanoparticles to the brain with minimal systemic exposure.
| S-EPMC6138562 | biostudies-literature
Project description:MicroRNAs (miRNAs/miRs) are known to be involved in various human cancer types. Ultrasound-targeted microbubble destruction (UTMD) may improve the transfection efficiency of exogenous genes into target tissues and organs, thereby improving cancer treatment. In the present study, the role of miR-4284 in non-small cell lung cancer (NSCLC) was investigated and the effect of UTMD-mediated inhibition of miR-4284 on tumor progression was further analyzed. The expression of miR-4284 in NSCLC cells and tissues was detected by reverse transcription-quantitative PCR. UTMD-mediated inhibition of miR-4284 was achieved by co-transfection of microvesicles and miR-4284 inhibitors into NSCLC cells. A Cell Counting Kit-8 assay was used to determine NSCLC cell proliferation, and the migration and invasion of NSCLC cells were examined by Transwell assays. Compared with that in the control group, the expression of miR-4284 was increased in NSCLC tissues and cells. Knockdown of miR-4284 in NSCLC cells inhibited cell proliferation, migration and invasion. UTMD improved the transfection efficiency of miR-4284 inhibitors in NSCLC cells, resulting in more significant inhibition of tumor cell proliferation, migration and invasion. In conclusion, the results indicated that the expression of miR-4284 was increased in clinical samples and cell lines of NSCLC and that knockdown of miR-4284 inhibited the proliferation, migration and invasion of tumor cells. UTMD-mediated miR-4284 inhibition further promoted this effect, indicating that this technique may represent a novel strategy for the treatment of NSCLC.
| S-EPMC8027739 | biostudies-literature