scholarly journals Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Yanlong Jia ◽  
Chaochao Wang ◽  
Jiehua Zheng ◽  
Guisen Lin ◽  
Dalong Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Chemical Exchange ◽  
Raft Polymerization ◽  
Animal Experiments ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Cest Imaging

Abstract Background Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. Results To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 μg/mL vs. ~ 5 μg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). Conclusions The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

scholarly journals Presaturation Power Adjusted Pulsed CEST: A Method to Increase Independence of Target CEST Signals

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Kazufumi Kikuchi ◽  
Keisuke Ishimatsu ◽  
Shanrong Zhang ◽  
Ivan E. Dimitrov ◽  
Hiroshi Honda ◽  
...  
Keyword(s):  
Exchange Rates ◽  
Chemical Exchange ◽  
Renal Medulla ◽  
Chemical Exchange Saturation Transfer ◽  
Amide Proton ◽  
Saturation Transfer ◽  
Cest Imaging ◽  
Concentration Changes

Chemical exchange saturation transfer (CEST) imaging has been demonstrated to discuss the concentration changes of amide proton, glutamate, creatine, or glucose measured at 3.5, 3.0, 2.0, and 1.0–1.2 ppm. However, these peaks in z-spectra are quite broad and overlap with each other, and thus, the independence of a CEST signal on any specific metabolite is still open to question. Here, we described whether there was interference among the CEST signals and how these CEST signals behave when the power of the presaturation pulse was changed. Based on these results, further experiments were designed to investigate a method to increase the independence of the CEST signal in both phantoms and animals. The result illustrates a clear interference among CEST signals. A presaturation power adjusted pulsed- (PPAP-) CEST method which was designed based on the exchange rates of the metabolites can be used to remove contributions from other exchanging species in the same sample. Further, the method was shown to improve the independence of the glutamate signal in vivo in the renal medulla in mice. The PPAP-CEST method has the potential to increase the independence of any target CEST signals in vivo by choosing the appropriate combination of pulse amplitudes and durations.

scholarly journals Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Farnaz Dabbagh Moghaddam ◽  
Iman Akbarzadeh ◽  
Ehsan Marzbankia ◽  
Mahsa Farid ◽  
Leila khaledi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cell Lines ◽  
Encapsulation Efficiency ◽  
Inbred Mice ◽  
Breast Cancer Treatment ◽  
Anticancer Effect ◽  
Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

Antineoplastic Activity of Products Derived From Cellulose-containing Materials: Study of Levoglucosenone and Structurally-related Analogous as New Alternatives for Breast Cancer Treatment

2021 ◽  
Author(s):  
Damian Ignacio Delbart ◽  
German Francisco Giri ◽  
Agostina Cammarata ◽  
Lizeth Ariza Bareño ◽  
Natalia Loreley Amigo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Breast Cancer Treatment ◽  
Soybean Hulls ◽  
Mitochondrial Potential ◽  
Cell Content ◽  
Lung Colonization ◽  
Ethidium Bromide Staining

Abstract Purpose: Breast cancer is the leading cause of cancer death among women worldwide. For this reason, the development of new therapies is still essential. In this work we have analyzed the antitumor potential of levoglucosenone, a chiral building block derived from glucose, and three structurally related analogues obtained from soybean hulls pyrolysis.Methods: Employing human and murine mammary cancer models, we have evaluated the effect of our compounds on cell viability through MTS assay, apoptosis induction by acridine orange / ethidium bromide staining and/or flow cytometry and the loss of mitochondrial potential by tetramethylrhodamine methyl ester staining. Autophagy and senescence induction were also evaluated by Western blot and β-galactosidase activity respectively. Secreted metalloproteases activity was determined by quantitative zymography. Migratory capacity was assessed by wound healing assays while invasive potential was analyzed using Matrigel-coated transwell chambers. In vivo studies were also performed to evaluate subcutaneous tumor growth and experimental lung colonization.Results: Apoptosis was identified as the main mechanism responsible for the reduction of monolayer cell content induced by the compounds without detecting modulations of autophagy or senescence processes. Two of the four compounds were able to modulate in vitro events associated with tumor progression, such as migratory potential, invasiveness, and proteases secretion. Furthermore, tumor volume and metastatic spread were significantly reduced in vivo after treatment with the compounds.Conclusion: We could obtain from soybean hulls, a material with almost no commercial value, a variety of chemical compounds useful for breast cancer treatment.

scholarly journals Monitoring food digestion with magnetic resonance techniques

2020 ◽  
pp. 1-11
Author(s):  
Paul A. M. Smeets ◽  
Ruoxuan Deng ◽  
Elise J. M. van Eijnatten ◽  
Morwarid Mayar
Keyword(s):  
Magnetic Resonance ◽  
Food Systems ◽  
Chemical Exchange ◽  
Quantitative Information ◽  
Model Systems ◽  
Chemical Exchange Saturation Transfer ◽  
Food Properties ◽  
Health And Disease

This review outlines the current use of magnetic resonance (MR) techniques to study digestion and highlights their potential for providing markers of digestive processes such as texture changes and nutrient breakdown. In vivo digestion research can be challenging due to practical constraints and biological complexity. Therefore, digestion is primarily studied using in vitro models. These would benefit from further in vivo validation. NMR is widely used to characterise food systems. MRI is a related technique that can be used to study both in vitro model systems and in vivo gastro-intestinal processes. MRI allows visualisation and quantification of gastric processes such as gastric emptying and coagulation. Both MRI and NMR scan sequences can be configured to be sensitive to different aspects of gastric or intestinal contents. For example, magnetisation transfer and chemical exchange saturation transfer can detect proton (1H) exchange between water and proteins. MRI techniques have the potential to provide molecular-level and quantitative information on in vivo gastric (protein) digestion. This requires careful validation in order to understand what these MR markers of digestion mean in a specific digestion context. Combined with other measures they can be used to validate and inform in vitro digestion models. This may bridge the gap between in vitro and in vivo digestion research and can aid the optimisation of food properties for different applications in health and disease.

scholarly journals Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 17 ◽  
Author(s):  
Maryam Nakhjavani ◽  
Jennifer E Hardingham ◽  
Helen M Palethorpe ◽  
Yoko Tomita ◽  
Eric Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Metastatic Breast ◽  
Therapeutic Agents ◽  
Ginsenoside Rg3 ◽  
Cancer Models ◽  
Anti Cancer ◽  
Ginseng Plant

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-cancer treatment for breast cancer will be reviewed.

scholarly journals Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer

2013 ◽  
Vol 71 (1) ◽  
pp. 164-172 ◽  
Author(s):  
Feliks Kogan ◽  
Mohammad Haris ◽  
Anup Singh ◽  
Kejia Cai ◽  
Catherine Debrosse ◽  
...  
Keyword(s):  
High Resolution ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
High Resolution Imaging ◽  
Saturation Transfer ◽  
Resolution Imaging
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