scholarly journals Starvation-Sensitized and Oxygenation-Promoted Tumor Sonodynamic Therapy by a Cascade Enzymatic Approach

Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Wencheng Wu ◽  
Yinying Pu ◽  
Han Lin ◽  
Heliang Yao ◽  
Jianlin Shi
Keyword(s):  
Tumor Cells ◽  
Tumor Hypoxia ◽  
Monomethyl Ether ◽  
Sonodynamic Therapy ◽  
Protective Mechanisms ◽  
Glucose Depletion ◽  
Therapeutic Outcomes ◽  
The Us ◽  
Energy Deprivation

The therapeutic outcomes of noninvasive sonodynamic therapy (SDT) are always compromised by tumor hypoxia, as well as inherent protective mechanisms of tumor. Herein, we report a simple cascade enzymatic approach of the concurrent glucose depletion and intratumoral oxygenation for starvation-sensitized and oxygenation-amplified sonodynamic therapy using a dual enzyme and sonosensitizer-loaded nanomedicine designated as GOD/CAT@ZPF-Lips. In particular, glucose oxidase- (GOD-) catalyzed glycolysis would cut off glucose supply within the tumor, resulting in the production of tumor hydrogen peroxide (H2O2) while causing tumor cells starvation. The generated H2O2 could subsequently be decomposed by catalase (CAT) to generate oxygen, which acts as reactants for the abundant singlet oxygen (1O2) production by loaded sonosensitizer hematoporphyrin monomethyl ether (HMME) upon the US irradiation, performing largely elevated therapeutic outcomes of SDT. In the meantime, the severe energy deprivation enabled by GOD-catalyzed glucose depletion would prevent tumor cells from executing protective mechanisms to defend themselves and make the tumor cells sensitized and succumbed to the cytotoxicity of 1O2. Eventually, GOD/CAT@ZPF-Lips demonstrate the excellent tumoral therapeutic effect of SDT in vivo without significant side effect through the cascade enzymatic starvation and oxygenation, and encouragingly, the tumor xenografts have been found completely eradicated in around 4 days by the intravenous injection of the nanomedicine without reoccurrence for as long as 20 days.

scholarly journals Biodegradable reduce expenditure bioreactor for augmented sonodynamic therapy via regulating tumor hypoxia and inducing pro-death autophagy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weijuan Zou ◽  
Junnian Hao ◽  
Jianrong Wu ◽  
Xiaojun Cai ◽  
Bing Hu ◽  
...  
Keyword(s):  
Tumor Hypoxia ◽  
Monomethyl Ether ◽  
In Vitro Assays ◽  
Sonodynamic Therapy ◽  
Mesoporous Organosilica ◽  
Hypoxic Tumor ◽  
Poly Ethylene ◽  
Excessive Activation

Abstract Backgrounds Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor strategy is challenged by the rapid depletion of oxygen, as well as the hypoxic tumor microenvironment. Instead of the presently available coping strategies that amplify the endogenous O2 level, we have proposed a biodegradable O2 economizer to reduce expenditure for augmenting SDT efficacy in the present study. Results We successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) via conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (hematoporphyrin monomethyl ether; HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia conditions. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induced excessive activation of autophagy for promoting the therapeutic efficacy. As a result, when accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP could achieve the remarkable antitumor activity, which was systematically validated both in vivo and in vitro assays. Conclusions This work not only provides a reduce expenditure means for enduring SDT, but also represents an inquisitive strategy for tumor treatments by inducing pro-death autophagy. Graphical Abstract

scholarly journals EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Akihiro Inoue ◽  
Daisuke Yamashita ◽  
Masahiro Nishikawa ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Normal Brain ◽  
Sonodynamic Therapy ◽  
Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

scholarly journals Biodegradable Reduce Expenditure Bioreactor For Augmented Sonodynamic Therapy Via Regulating Tumor Hypoxia And Inducing Pro-Death Autophagy

2021 ◽  
Author(s):  
Weijuan Zou ◽  
Junnian Hao ◽  
Jianrong Wu ◽  
Xiaojun Cai ◽  
Bing Hu ◽  
...  
Keyword(s):  
Tumor Hypoxia ◽  
In Vitro Assays ◽  
Poly Ethylene Glycol ◽  
Sonodynamic Therapy ◽  
Mesoporous Organosilica ◽  
Hypoxic Tumor ◽  
Poly Ethylene ◽  
Excessive Activation

Abstract Backgrounds: Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor means is still hampered by the rapid depletion of oxygen, as well as hypoxic tumor microenvironment. Instead of the currently coping strategies through amplifying endogenous O2 level, herein, a biodegradable O2 economizer is described as a reduce expenditure bioreactor for augmenting SDT efficacy. Results: We have successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) by the conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induce excessive activation of autophagy for promoting the therapeutic efficacy. As a result, accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP achieves remarkable antitumor activity, which has been systematically validated both in vivo and in vitro assays. Conclusion: This work not only provides a reduce expenditure strategy for enduring SDT, but also represents an inquisitive strategy for tumor treatments via inducing pro-death autophagy.

scholarly journals A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yiling Yang ◽  
Shaohua Hua ◽  
Weilong Suo ◽  
Wenbin Wang ◽  
Longhao Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Tissue ◽  
Tumor Hypoxia ◽  
Inhibitory Effect ◽  
Sonodynamic Therapy ◽  
Tumor Cell Membrane ◽  
Therapeutic Measure ◽  
Oxygen Generation ◽  
Hypoxic State

Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the employment of a sonosensitizing curcumin (Cur) load embedded within a MnO2 core, together with an extraneous tumor cell membrane component. The latter allows for efficient tumor recognition properties. Hollowed-out MnO2 allows for efficient drug delivery, together with catalyzing oxygen generation from hydrogen peroxide present in tumor tissue, leading to enhanced SDT efficacy through the induction of a reduced hypoxic state within the tumor. In addition, Cur acts as a cytotoxic agent in its own right. The results deriving from in vivo studies revealed that such a biomimetic approach for drug-delivery actually led to a reduced hypoxic state within tumor tissue and a raised tumor-inhibitory effect within mouse models. Such a therapeutic measure attained a synergic SDT-based tumor sensitization treatment option, together with the potential use of such catalysis-based therapeutic formulations in other medical conditions having hypoxic states.

scholarly journals Selectively Targeting Tumor Hypoxia with the Hypoxia-Activated Prodrug CP-506

2021 ◽  
Author(s):  
Alexander M.A. van der Wiel ◽  
Victoria Jackson-Patel ◽  
Raymon Niemans ◽  
Ala Yaromina ◽  
Emily Liu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Tumor Hypoxia ◽  
Human Tumor ◽  
Tumor Oxygenation ◽  
Antitumor Effects ◽  
Wide Range ◽  
Hypoxic Tumor

Abstract Background Hypoxia-activated prodrugs (HAPs) are a promising class of antineoplastic agents that can selectively eliminate hypoxic tumor cells. The present study evaluates the hypoxia-selectivity and antitumor activity of CP-506, a DNA alkylating HAP with favorable pharmacological properties. Methods Stoichiometry of reduction, one-electron affinity, and back-oxidation rate of CP-506 were characterized by fast-reaction radiolytic methods. In vitro, 2D monolayer and 3D spheroid and multicellular layer cultures were used to investigate the hypoxia-selectivity of CP-506. In vivo, the causal relationship between tumor oxygenation and antitumor effects of CP-506 was assessed. Mice bearing a range of human tumor xenografts were exposed to CP-506 and tumor growth was monitored. A multivariate linear regression model was used to identify factors associated with CP-506 treatment outcome. Results Net reduction, metabolism, and cytotoxicity of CP-506 were maximally inhibited at oxygen concentrations above 1 µM (0.1% O2). CP-506 demonstrated cytotoxicity selectively in hypoxic 2D and 3D cell cultures with normoxic/anoxic IC50 ratios up to 203. In vivo, the antitumor effects of CP-506 were selective for hypoxic tumor cells and causally related to tumor oxygenation. CP-506 effectively decreased the hypoxic fraction and inhibited growth of a wide range of hypoxic xenografts. Two well-oxygenated models were refractory to treatment despite intrinsic anoxic sensitivity in vitro. A multivariate regression analysis revealed baseline tumor hypoxia and in vitro sensitivity to CP-506 to significantly correlate with treatment response. Conclusions Our results demonstrate that CP-506 selectively sterilizes hypoxic tumor cells and has broad antitumor activity. Our data also indicate that tumor hypoxia and cellular sensitivity to CP-506 are strong determinants of the antitumor effects of CP-506.

The Expression of Erythropoietin and Its Receptor in Breast Cancer Is Associated with In Vivo Tumor Hypoxia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4256-4256
Author(s):  
Murat O. Arcasoy ◽  
Khalid Amin ◽  
Shu-Chuan Chou ◽  
Ruth Lininger ◽  
James A. Raleigh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Primary Breast Cancer ◽  
Breast Cancer Cells ◽  
Significant Positive Correlation ◽  
Tumor Hypoxia ◽  
N 93 ◽  
Epor Expression

Abstract Erythropoietin (EPO) is primarily produced in the adult kidney where hypoxia is the major stimulus for EPO expression under the control of an oxygen-sensing mechanism. A series of previous studies in our laboratories and others have demonstrated the expression of EPO and its receptor (EPOR) in breast cancer cells. In previous work, we found that the administration of antagonists of EPO-EPOR signaling was associated with delayed tumor growth in a rodent syngeneic breast cancer model, suggesting the presence of a functional EPO-EPOR system in cancer. The mechanisms of EPO and EPOR expression in tumor cells requires further study. In vitro experiments using monolayer cultures of breast cancer cells have suggested that EPO and EPOR expression in tumor cells may be hypoxia-regulated. The objective of our current studies was to determine the relationship between the expression of EPO, EPOR and tumor hypoxia in breast cancer to test the hypothesis that EPO or EPOR expression in malignant cells may be associated with the presence of in vivo tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness and poor prognosis. Thirty-eight patients with primary breast cancer were enrolled in a tumor hypoxia study under a research protocol approved by the Institutional Review Board at the University of North Carolina Hospitals. All patients provided signed informed consent. The patients received an intravenous infusion of the hypoxia marker pimonidazole hydrochloride (Hypoxyprobe-1™) prior to tumor biopsy. Two or more biopsies were obtained from 33 tumors and 5 primary tumors had a single biopsy available. Contiguous sections from a total of 93 biopsies were analyzed by immunohistochemistry using monoclonal antibodies for the expression of EPO and EPOR and pimonidazole binding. We found EPO expression in tumor cells in 94% of the biopsies. Focal EPO expression pattern was observed in many tumors. EPOR expression was present in 93% of biopsies. The pattern of EPOR immunoreactivity was predominantly cytoplasmic but was found to be localized to the membrane in some sections. In many tumors, co-localization of EPO and EPOR expression in tumor cells was present when contiguous sections were examined. Tumor hypoxia was detected in 83% of the biopsies at variable levels and did not always co-localize with EPO or EPOR expression in tumor cells. Semi-quantitative analyses for EPO immunostaining and tumor hypoxia on a section-by-section basis revealed a significant positive correlation between levels of micro-regional EPO expression and pimonidazole binding (r = 0.6, P &lt; 0.0001, n=93 by two-tailed Spearman’s rank correlation analysis). A similar significant positive correlation was found between levels of EPOR expression and pimonidazole binding (r = 0.63, P &lt; 0.0001, n=93). In addition, there was a significant association between the semi-quantitative EPO score in tumor cells and the EPOR score (r = 0.6, P &lt; 0.0001, n=93). We also determined the micro-vessel density (MVD), a marker of tumor angiogenesis, in 35 biopsies using factor VIII immunostaining. There was no correlation between EPO or EPOR expression and MVD in these samples. In conclusion, these data demonstrate for the first time that EPO and EPOR expression in breast cancer cells correlates with in vivo tumor hypoxia in clinical specimens of primary breast cancer.

EXTH-41. IMPROVING THE RADIOSENSITIVITY OF DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPG) BY TARGETING HYPOXIA AND MITOCHONDRIAL METABOLISM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi172-vi172
Author(s):  
Han Shen ◽  
Cecilia Chang ◽  
Prunella Ing ◽  
Kristina Cook ◽  
Kelly McKelvey ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Cells ◽  
Combination Treatment ◽  
High Throughput Screening ◽  
Tumor Hypoxia ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Protein Levels ◽  
Approved Drugs

Abstract DIPG is the leading cause of brain tumor-related death in children. Radiotherapy is the only treatment that offers transient benefit and provides palliative care. DIPGs are hypo-perfused with tumor cells being exposed to hypoxia, a potent barrier to effective radiotherapy. Reducing the oxygen consumption rate (OCR) is therefore a potential strategy to reduce tumor hypoxia. We therefore performed a high-throughput screening with 1963 FDA-approved drugs that could reduce tumor hypoxia and OCR, thereby improving radiosensitivity of DIPGs. A subset of anti-diabetic drugs was identified, with phenformin amongst the most potent. It significantly reduced OCR in a panel of DIPG cultures and subsequently suppressed hypoxia in 3-dimensional DIPG neurosphere models that mimic the hypoxic microenvironment. In addition, phenformin demonstrated greater anti-tumor activity and radiosensitizing effect with much lower doses compared with metformin, a less potent biguanide that improved radiosensitivity of DIPG in a patient-derived xenograft (PDX) model in our previous study. The effect of phenformin was further enhanced by combining a second drug dichloroacetate that simultaneously attenuated phenformin-induced acidification rate. Specifically, the combination of phenformin and dichloroacetate induced higher levels of hypoxia inhibition, reactive oxygen species, DNA damage and apoptosis. RNA sequencing demonstrated significant changes induced by the combination treatment in cell-cycle, DNA repair, unfolded protein response and alternative energetic pathways. These changes were further validated by PCR array and western blotting at mRNA and protein levels. In addition, two master regulators that enhance the metabolic capacity of tumor cells through increased glycolysis thus contributing to radioresistance, HIF-1α and c-Myc, were also significantly suppressed by combination treatment. Ultimately, the triple combination of phenformin, DCA and irradiation demonstrated the most potent efficacy in inducing DNA damage, apoptosis and clonogenic inhibition in DIPG cultures. This promising triple combination therapy is currently being tested in our PDX cohort in vivo.

scholarly journals Preclinical and Nonclinical Characterization of HPN217: A Tri-Specific T Cell Activating Construct (TriTAC) Targeting B Cell Maturation Antigen (BCMA) for the Treatment of Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3225-3225 ◽  
Author(s):  
Che-Leung Law ◽  
Wade Aaron ◽  
Rick Austin ◽  
Manasi Barath ◽  
Evan Callihan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cell ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Half Life ◽  
Cell Activation ◽  
The Us ◽  
Dose Dependent

Abstract About 31,000 new cases of multiple myeloma (MM) will be diagnosed in the US in 2018. In addition to chemotherapeutic agents, several targeted therapies utilizing distinct mechanisms of action, e.g., proteasome inhibitors (bortezomib, carfilzomib, ixazomib), HDAC inhibitors (panobinostat), Cullin-RING E3 ubiquitin ligase activators (thalidomide, lenalidomide, pomalidomide), and antibodies (daratumumab, elotuzumab) have become available for treating MM. However, MM remains an incurable disease. Patients who relapse after or are refractory to standard of care treatments generally have poor prognosis. In 2018, close to 13,000 patients will die of the disease in the US. Targeting the B cell maturation antigen (BCMA), a BAFF/BLyS and APRIL receptor, for treating MM patients can provide a new treatment approach complementary to existing therapies. CAR-T therapies and an antibody-drug conjugate targeting BCMA have demonstrated early clinical success in the treatment of relapsed refractory MM (RRMM). HPN217 is a tri-specific T cell activating construct (TriTAC) consisting of three binding domains: an N-terminal single domain antibody (sdAb) that binds to human BCMA, a middle sdAb that binds to human serum albumin (HSA), and a C-terminal single chain Fv (scFv) that binds to CD3ε of the T cell receptor (TCR) complex. HPN217 is a highly stable single polypeptide of ~ 53 kDa expressed by CHO cells. Simultaneous engagement of BCMA on a target MM cell and CD3 on a T cell results in T cell activation, functional differentiation and the eventual lysis of the target MM cell. Engineering of an HSA binding domain into HPN217 represents a unique strategy in extending serum half-life, giving the TriTAC molecule a small molecular size and flexibility. This approach is different from Fc-engineering applied in other CD3-based bispecific T cell engaging molecules. The KD of HPN217 binding to recombinant human BCMA, HSA, and recombinant human CD3ε was determined to be 5.5 nM, 6 nM, and 17 nM, respectively, as measured by biolayer interferometry. Flow cytometric analysis on a panel of T cells from normal donors and BCMA positive and BCMA negative tumor cell lines confirmed binding of HPN217 to its native targets expressed on cell surface. The in vitro pharmacological activity of HPN217 was evaluated by T cell-dependent cellular cytotoxicity (TDCC) assays. In co-cultures of T cells from normal human or cynomolgus monkey donors, target tumor cells, and HSA, HPN217 mediated dose-dependent and BCMA-dependent cytotoxicity with EC50 values ranging from 0.05 to 0.7 nM. Killing was dependent on expression of BCMA on target tumor cells. Concomitant with target tumor cell killing, HPN217 also mediated dose-dependent upregulation of CD25 and CD69 on T cells in the TDCC co-cultures when BCMA positive tumor cells were presence. Consistent with the mechanism of action of CD3-based T cell engaging molecules, T cell derived cytokines, e.g., TNFα and IFNγ, were detected. Similar T cell activation could be observed using human or cynomolgus monkey whole blood as a source of T cells. Nonclinical in vivo properties of HPN217 were evaluated in xenograft models and a single dose pharmacokinetic (PK) study in cynomolgus monkeys. HPN217 mediated dose-dependent growth suppression against the RPMI-8226 MM model and Jeko-1 mantle cell lymphoma model expressing relatively low levels of 5,600 and 2,200 copies of BCMA per cell, respectively. In the PK study, a single dose of HPN217 at 0.01, 0.1, or 1 mg/kg was given to cynomolgus monkeys. HPN217 exhibited linear PK behavior over this dose range. Serum half-life was in the range of 64 to 85 hours. Serum half-life, volume of distribution, and clearance appeared to be independent of dose. HPN217 was demonstrated to be stable and remained intact up to 3 weeks in vivo as demonstrated by a functional ligand binding assay using recombinant CD3ε and BCMA, respectively, to capture and detect HPN217. Importantly, serum samples collected one week after dosing were as potent as stock HPN217 in MM tumor cell killing in TDCC assays. Collectively, preclinical and nonclinical characterization suggests that HPN217 is an efficacious novel therapeutic candidate that can provide a convenient dosing schedule for patients. A first-in-human phase 1 clinical trial is planned to evaluate HPN217 in RRMM. Disclosures Law: Harpoon Therapeutics: Employment. Aaron:Harpoon Therapeutics: Employment. Austin:Harpoon Therapeutics: Employment. Barath:Harpoon Therapeutics: Employment. Callihan:Harpoon Therapeutics: Employment. Evans:Harpoon Therapeutics: Employment. Gamez Guerrero:Harpoon Therapeutics: Employment. Hemmati:Harpoon Therapeutics: Employment. Jones:Harpoon Therapeutics: Employment. Kwant:Harpoon Therapeutics: Employment. Lao:Harpoon Therapeutics: Employment. Lemon:Harpoon Therapeutics: Employment. Patnaik:Harpoon Therapeutics: Employment. Sexton:Harpoon Therapeutics: Employment. Wesche:Harpoon Therapeutics: Employment. Xiao:Harpoon Therapeutics: Employment. Yu:Harpoon Therapeutics: Employment. Yu:Harpoon Therapeutics: Employment.

scholarly journals Using C-doped TiO2 Nanoparticles as a Novel Sonosensitizer for Cancer Treatment

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 880 ◽  
Author(s):  
Chun-Chen Yang ◽  
Chong-Xuan Wang ◽  
Che-Yung Kuan ◽  
Chih-Ying Chi ◽  
Ching-Yun Chen ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Tumor Cells ◽  
Titanium Dioxide Nanoparticles ◽  
Sol Gel ◽  
Inorganic Materials ◽  
Sonodynamic Therapy ◽  
Carbon Doped ◽  
Significant Difference ◽  
Doped Titanium Dioxide

Sonodynamic therapy is an effective treatment for eliminating tumor cells by irradiating sonosentitizer in a patient’s body with higher penetration ultrasound and inducing the free radicals. Titanium dioxide has attracted the most attention due to its properties among many nanosensitizers. Hence, in this study, carbon doped titanium dioxide, one of inorganic materials, is applied to avoid the foregoing, and furthermore, carbon doped titanium dioxide is used to generate ROS under ultrasound irradiation to eliminate tumor cells. Spherical carbon doped titanium dioxide nanoparticles are synthesized by the sol-gel process. The forming of C-Ti-O bond may also induce defects in lattice which would be beneficial for the phenomenon of sonoluminescence to improve the effectiveness of sonodynamic therapy. By dint of DCFDA, WST-1, LDH and the Live/Dead test, carbon doped titanium dioxide nanoparticles are shown to be a biocompatible material which may induce ROS radicals to suppress the proliferation of 4T1 breast cancer cells under ultrasound treatment. From in vivo study, carbon doped titanium dioxide nanoparticles activated by ultrasound may inhibit the growth of the 4T1 tumor, and it showed a significant difference between sonodynamic therapy (SDT) and the other groups on the seventh day of the treatment.

Phycocyanin Nanoparticle as a Novel Sonosensitizer for Tumor Sonodynamic Therapy of Michigan Cancer Foundation-7 Cells In Vitro

2021 ◽  
Vol 21 (5) ◽  
pp. 3035-3040
Author(s):  
Jin Cao ◽  
Qiwen Pan ◽  
Mingxue Zheng ◽  
Song Shen ◽  
Xueyong Qi
Keyword(s):  
Cancer Cell Line ◽  
Monomethyl Ether ◽  
Cell Uptake ◽  
Ros Generation ◽  
Human Breast ◽  
Sonodynamic Therapy ◽  
Poor Stability ◽  
Mcf 7

The development of novel sonosensitizers with safety and efficiency is a key problem in anti-tumor sonodynamic therapy. Phycocyanin (PC) has been proved to have the singlet oxygen radicals (ROS) generation ability, and the potential of PC as a novel sonosensitizer has been investigated. To overcome the disadvantages of PC in vivo, such as poor stability and low half-life, PC nanoparticles (PCNP) were prepared by the cross-linking method. According to the results, PCNP has been found with good morphology, good particle size distribution and good stability. Human breast cancer cell line MCF-7 was used to investigate PCNP cell uptake ability. ROS generation and cytotoxicity under ultrasonic irradiation (sonotoxicity) were also studied on this cell. Under the condition of 0.75 w/cm2 ultrasound, PCNP has a good ROS productivity and is equivalent to the sonotoxicity of the known sonosensitizer hematoporphyrin monomethyl Ether (HMME). In conclusion, PCNP is expected to be developed as an effective sonosensitizer for the sonodynamic therapy of tumors.

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