Applications of magnetoliposomes with encapsulated doxorubicin for integrated chemotherapy and hyperthermia of rat C6 glioma

2018 ◽  
Vol 73 (7-8) ◽  
pp. 265-271 ◽  
Author(s):  
Natália Babincová ◽  
Paul Sourivong ◽  
Peter Babinec ◽  
Christian Bergemann ◽  
Melánia Babincová ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Cell Viability ◽  
Targeted Delivery ◽  
Combined Treatment ◽  
Chemotherapeutic Agents ◽  
Alternating Magnetic Field ◽  
Magnetic Drug Targeting ◽  
Complete Regression

Abstract There is substantial evidence regarding enhanced antitumor cytotoxicity of selected chemotherapeutic agents by appropriate heat exposure (40–44°C). Based upon these results, the integration of hyperthermia as an additional treatment modality given simultaneously with systemic chemotherapy is currently of considerable interest. Hyperthermia can be induced by alternating magnetic field and magnetic nanoparticles. Thus, we have used thermosensitive magnetoliposomes that contained superparamagnetic iron oxide nanoparticles and doxorubicin for in vitro and in vivo therapy of rat glioma C6. The results showed that magnetoliposomes can be specifically heated to 43°C (phase transition temperature of a used lipid composition) in a few minutes, and during this, the encapsulated doxorubicin is released in a controllable manner. The in vitro experiments showed that the cell viability decreased to 79.2% after heat treatment alone and to 47.4% for doxorubicin-loaded magnetoliposomes without application of alternating magnetic field, while the combined treatment resulted in 17.3% cell viability. Also, in vivo results demonstrated that magnetic drug targeting has a strong antiglioma effect with a tumor volume growth inhibition and complete regression. Such targeted delivery and controlled release of anticancer agents would provide clinical advantages compared with currently available methods.

Nanoparticle-targeted delivery of nonanticoagulant heparin and doxorubicin in doxorubicin-resistant breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11599-e11599
Author(s):  
D. J. Bharali ◽  
M. Yalcin ◽  
U. Dier ◽  
S. Mousa ◽  
S. Mousa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Double Emulsion ◽  
Chemotherapeutic Agents ◽  
Confocal Imaging ◽  
Breast Cancer Patients ◽  
Cell Viability Assay ◽  
Custom Made

e11599 Background: In comparison to low molecular weight heparin (LMWH), non-anticoagulant heparin (NACH), originally developed in our laboratory, has minimal effects on hemostasis. Encapsulation of chemotherapeutic agents and NACH in biodegradable nanoparticles has tremendous potential in improving survival among the breast cancer patients. Furthermore, custom-made nanoparticles with a targeted moiety on the surface would enable us to increase the efficacy and decrease the adverse effects of doxorubicin. Methods: PLGA-PEG nanoparticles co-encapsulating NACH and doxorubicin were synthesized by double emulsion solvent evaporation method. The in vitro efficacy of these nanoparticles was examined in MCF-7 doxorubicin resistant (MCF-7R) cells using MTT cell viability assay. Confocal microscopy was used to examine the uptake of αvβ3 antibody conjugated nanoparticles in human dermal microvascular endothelial cells (HDMEC), which are known to over express αvβ3 integrins. Results: Size measurement by DLS revealed that these nanoparticles co-encapsulating doxorubicin and heparins to be 200–300 nm in size. Data from the MTT assays in MCF-7R cells showed synergy between NACH and doxorubicin when encapsulated in PLGA-PEG nanoparticles. Confocal imaging in HDMEC cells indicates that these nanoparticles have the potential to be used for site specific delivery to the tumor neovascularization. In vivo data in nude mice xenograft (MCF-7R) are shown in the table below (doses of doxorubicin and NACH injected subcutaneously were 0.625 mg/kg and 2.5 mg/kg body weight, respectively). Significant decrease in tumor weight was observed in the mice xenograft, when treated with αvβ3 conjugated nanoparticles co-encapsulating doxorubcin or to greater extent doxorubicin and NACH compares to its non encapsulated counterparts. Conclusions: These data indicated distinct improvement in the anti-tumor efficacy using αvβ3site directed delivery doxorubicin and NACH encapsulted in PLGA-PEG nanoparticles. [Table: see text] No significant financial relationships to disclose.

Abstract No. 122: Alternating magnetic field thermotherapy of liver tumors: preliminary in vitro and in vivo study

2012 ◽  
Vol 23 (3) ◽  
pp. S51-S52
Author(s):  
E. Liapi ◽  
S. Mirpour ◽  
M. Wabler ◽  
H. Zhou ◽  
Y. Zhang ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Liver Tumors ◽  
Alternating Magnetic Field ◽  
In Vivo Study

scholarly journals SOX4 promotes the growth and metastasis of breast cancer

2020 ◽  
Author(s):  
Jing Zhang ◽  
Chunhua Xiao ◽  
Zhenbo Feng ◽  
Yun Gong ◽  
Baohua Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Lymph Nodes ◽  
Cell Viability ◽  
Cancer Cell ◽  
Chemotherapeutic Agents ◽  
Migration And Invasion ◽  
Primary Tumors

Abstract Purpose Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo . Methods We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging. Results SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo . It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel. Conclusions SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

Synthesis and In vitro/In vivo Characterization of Raloxifene Grafted Poly(Styrene Maleic Acid)-Poly(Amide-Ether-Ester-Imide) Micelles for Targeted Delivery of Docetaxel in G Protein-Coupled Estrogen Receptor Breast Cancer

2019 ◽  
Vol 18 (14) ◽  
pp. 2017-2031 ◽  
Author(s):  
Jaleh Varshosaz ◽  
Saeedeh Enteshari ◽  
Farshid Hassanzadeh ◽  
Batool Hashemi-Beni ◽  
Mohsen Minaiyan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Maleic Acid ◽  
Targeted Delivery ◽  
Chemotherapeutic Agents ◽  
Whole Body ◽  
Toxicity Tests ◽  
Severe Toxicity ◽  
Ether Ester

Background: To reduce the nonspecifically distribution of chemotherapeutic agents throughout the whole body, which causes severe toxicity in normal tissues, targeting them towards a receptor overexpressed on tumor tissue, is a promising method for cancer therapy. Objective: The aim of the present study was development of novel copolymeric micelles of raloxifene targeted Styrene Maleic Acid-Poly Amide Ether Ester Imide-Poly Ethylene Glycol (SMA-PAEEI-PEG-RA) and loading them with Docetaxel (DTX). Methods: Successful synthesis of the targeted copolymer was confirmed by FTIR and C-NMR spectroscopy. The micelles physicochemical properties like morphology, particle size, poly dispersity index, zeta potential, drug loading, release, stability, in vitro cytotoxicity and cellular uptake were analyzed. The in vivo antitumor activity of DTX-loaded micelles were assessed and compared with free DTX and non-targeted micelles in breast cancer bearing Balb-c mice. Results: Particle sizes, zeta potentials and the encapsulation efficiency of the drug in targeted micelles were 115.9- 142.8 nm, -4.9 to -12.9 mV, and 54.1-67.8%, respectively. Cell toxicity tests showed that IC50 of DTX-loaded SMAPAEEI- PEG-RA micelles increased five-fold as compared with free DTX. Survival rate of the mice improved more effectively than free DTX so that, the percentage of increase in lifespan (ILS%) and the tumor inhibition ratio (TIR) changed from 41.66% and 51.19% in free drug to 83.33% and 78.57% in the targeted micelles, respectively. Conclusion: Therefore, the raloxifene conjugated PEG-derived micelles may provide a novel and effective delivery system for DTX in breast cancer.

scholarly journals Anti-cancer properties of cannabidiol and Δ9-tetrahydrocannabinol and potential synergistic effects with gemcitabine, cisplatin and other cannabinoids in bladder cancer

2021 ◽  
Author(s):  
Andrea M Tomko ◽  
Erin G Whynot ◽  
Denis J Dupre
Keyword(s):  
Bladder Cancer ◽  
Cell Viability ◽  
Synergistic Effects ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Anti Cancer ◽  
Concentration Curves ◽  
Apoptotic Cascade

Introduction: With the legalization of cannabis in multiple jurisdictions throughout the world, a larger proportion of the population consumes cannabis. Several studies have demonstrated anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of cannabinoids in bladder cancer, and how cannabinoids could potentially synergize with chemotherapeutic agents. Our study aims to identify whether a combination of cannabinoids, like cannabidiol and Δ9-tetrahydrocannabinol with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, is able to produce desirable synergistic effects. We also evaluated whether co-treatment of different cannabinoids also generated synergistic effects. Materials and Methods: We generated concentration curves with different drugs to identify the range at which they could exert anti-tumor effects. We also evaluated the activation of the apoptotic cascade and whether cannabinoids have the ability to reduce invasion. Results: Cannabidiol, Δ9-tetrahydrocannabinol and other cannabinoids reduce cell viability of bladder cancer cell lines, and their combination with gemcitabine or cisplatin may induce differential responses: from antagonistic to additive and synergistic effects, depending on the concentrations used. Cannabidiol and Δ9-tetrahydrocannabinol were also shown to induce caspase 3 cleavage and reduce invasion in a Matrigel assay. Cannabidiol and Δ9-tetrahydrocannabinol also display synergistic properties with other cannabinoids like cannabichromene or cannabivarin. Discussion: Our results indicate that cannabinoids can reduce human bladder transitional cell carcinoma cell viability, and that they can potentially exert synergistic effects when combined with other agents. Our in vitro results will form the basis for future studies in vivo and in clinical trials for the development of new therapies that could be beneficial for the treatment of bladder cancer in the future.

scholarly journals Amlexanox Enhances Temozolomide-Induced Anti-Tumor Effects In Human Glioblastoma Cells By Inhibiting Ikbke And The Akt-mtor Signaling Pathway

2020 ◽  
Author(s):  
Jinbiao Xiong ◽  
Gaochao Guo ◽  
Lianmei Guo ◽  
Zengguang Wang ◽  
Zhijuan Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Viability ◽  
Glioma Cell ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Migration And Invasion ◽  
Cell Viability Assay ◽  
Primary Glioma

Abstract Background: Temozolomide (TMZ), as the first-line chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM), often fails to improve the prognosis of GBM patients due to the quick development of resistance. The need for more effective management of GBM is urgent. The aim of this study is to evaluate the efficacy of combined therapy with TMZ and amlexanox, a selective inhibitor of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), for GBM.Methods: in vitro, cell viability assay, apoptosis analysis, western blot, migration and invasion assay were used. In vivo, intracranial tumor models were constructed and the immunohistochemistry were used. Results: We found that combined treatment resulted in significant induction of cellular apoptosis and the inhibition of cell viability, migration and invasion in primary glioma cell and in the human glioma cell line, U87 MG. TMZ enhanced expression of phosphoration of adenosine 5‘-monophosphate-activated protein kinase (p-AMPK) and amlexanox led to reduction of IKBKE, with no impact on p-AMPK. Furthermore, we demonstrated that, compared to other groups treated with each component alone, TMZ combined with amlexanox effectively inhibited phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR). In addition, the combination treatment also clearly reduced in vivo tumor volume and prolonged median survival time in the xenograft mouse model. Conclusion: These results suggest that amlexanox sensitized primary glioma cell and U87 MG cell to TMZ at least partially though the suppression of IKBKE activation and the attenuation of AKT activation. Overall, combined treatment with TMZ and amlexanox may provide a promising possibility for improving the prognosis of glioblastoma patients in clinical practice.

Cytotoxic Stilbenes and Derivatives as Promising Antimitotic Leads for Cancer Therapy

2019 ◽  
Vol 24 (36) ◽  
pp. 4270-4311 ◽  
Author(s):  
Célia Faustino ◽  
Ana P. Francisco ◽  
Vera M. S. Isca ◽  
Noélia Duarte
Keyword(s):  
Cancer Therapy ◽  
Targeted Delivery ◽  
Biological Evaluation ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agents ◽  
Stable Configuration ◽  
Antiangiogenic Agents ◽  
Antitumor Effects

The growing incidence of cancer, the toxic side-effects associated with conventional chemotherapeutic agents and the development of multidrug resistance (MDR) drive the search for novel and more effective drugs with multi-target activity and selectivity towards cancer cells. Stilbenes are a group of naturally occurring phenolic compounds of plant origin derived from the phenylpropanoid pathway that may exist as cis- or trans-isomers. Although the trans-isomer is the more common and stable configuration, resveratrol being a representative compound, cis-stilbenes are potent cytotoxic agents that bind to and inhibit tubulin polymerization, destabilizing microtubules. This review summarizes the chemistry and biological evaluation of cytotoxic stilbenes and their synthetic derivatives as promising antimitotic leads for cancer therapy, focusing on the most potent compounds, the combretastatins. Combretastatins isolated from the South African bushwillow Combretum caffrum are among the most potent antimitotic and vascular disrupting agents (VDAs) of natural origin. Preclinical studies have demonstrated their potent antitumor effects in a wide variety of tumors, both in vitro and in vivo, being currently under evaluation in phase 2 and phase 3 clinical trials for several types of solid tumors. Topics covered herein include synthetic medicinal chemistry, modes of action, structure-activity relationships (SAR), preclinical and clinical studies as VDAs in cancer therapy, either as single agents or in combination with cytotoxic anticancer drugs, antiangiogenic agents, or radiation therapy, and development of appropriate formulations based on nanocarriers (e.g., liposomes, nanoemulsions, polymeric, lipid and ceramic nanoparticles, carbon nanotubes) for improved bioavailability and targeted delivery of combretastatins to the tumor vasculature.

scholarly journals Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

Medicines ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. 87 ◽  
Author(s):  
Francesco Petrella ◽  
Isabella Rimoldi ◽  
Stefania Rizzo ◽  
Lorenzo Spaggiari
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Tumour Microenvironment ◽  
Chemotherapeutic Agents ◽  
Immunomodulatory Activity ◽  
Neoplastic Cells

Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

In Vitro and In Vivo Characterization of Various Ferrites for Hyperthermia in Cancer-Treatment

2005 ◽  
Vol 284-286 ◽  
pp. 827-830
Author(s):  
D.H. Kim ◽  
Se Ho Lee ◽  
Kyoung Nam Kim ◽  
Kwang Mahn Kim ◽  
I.B. Shim ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Cancer Treatment ◽  
Carcinoma Cells ◽  
Alternating Magnetic Field ◽  
Normal Cells ◽  
Tumor Bearing ◽  
In Vivo Characterization

Ceramic ferrites can be used to cancer-treatment. Heating of certain organs or tissue up to temperature between 42oC and 45oC preferentially for cancer therapy is called hyperthermia. We synthesized ferrites with various compositions in the system Co1-xNixFe2O4 as hyperthermic thermoseed in cancer-treatment and evaluated their effects on the necrosis of cancer cells under alternating magnetic field in vivo as well as in vitro. When a CoFe2O4 was placed into 0.2 ml distilled water, the greatest temperature change in this study, Δ T=29.3oC, was observed. More than half of the carcinoma cells were dead after exposure to alternating magnetic field using CoFe2O4, while normal cells were survived more than 60%. The injection of this ferrite particles into the tumor bearing mice was able to suppress the number and volume of tumors. CoFe2O4 is expected the useful hyperthermic thermoseed in cancer-treatment because it exhibited the greatest necrosis of carcinoma cells in vitro and in vivo.

scholarly journals Transmittance measurements in non-alternating magnetic field as reliable method for determining of heating properties of Fe3O4 magnetic nanoparticles

2021 ◽  
Author(s):  
Magdalena Radović ◽  
Marija Mirković ◽  
Aleksandar S. Nikolić ◽  
Milorad Kuraica ◽  
Predrag Iskrenović ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Magnetic Nanoparticles ◽  
Radiochemical Purity ◽  
Biomedical Application ◽  
Alternating Magnetic Field ◽  
Hyperthermia Treatment ◽  
High Heating ◽  
Theranostic Agents

Abstract Different phosphates and phosphonates have shown excellent coating ability toward magnetic nanoparticles, improving their stability and biocompatibility which enables their biomedical application. The magnetic hyperthermia efficiency of phosphates (IDP and IHP) and phosphonates (MDP and HEDP) coated Fe3O4 magnetic nanoparticles (MNPs) were evaluated in an alternating magnetic field. For a deeper understanding of hyperthermia, the behavior of investigated MNPs in the non-alternating magnetic field was monitored by measuring the transparency of the sample. To investigate their theranostic potential coated Fe3O4-MNPs were radiolabeled with radionuclide 177Lu. Phosphate coated MNPs were radiolabeled in high radiolabeling yield (> 99%) while phosphonate coated MNPs reached maximum radiolabeling yield of 78%. Regardless lower radiolabeling yield both radiolabeled phosphonate MNPs may be further purified reaching radiochemical purity of more than 95%. In vitro stabile radiolabeled nanoparticles in saline and HSA were obtained. The high heating ability of phosphates and phosphonates coated MNPs as sine qua non for efficient in vivo hyperthermia treatment and satisfactory radiolabeling yield justifies their further research in order to develop new theranostic agents.

Sign in / Sign up

Export Citation Format

Share Document