Regulation of melanoma cell growth by a miR-21 loaded targeted delivery system based on microparticles and nanoparticles targeting phosphatase and tensin homolog (PTEN)

2021 ◽  
Vol 11 (11) ◽  
pp. 1766-1773
Author(s):  
Lei Jin ◽  
Tong Yang
Keyword(s):  
Delivery System ◽  
Self Assembly ◽  
Targeted Delivery ◽  
Melanoma Cells ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Assembly Method ◽  
New Strategy ◽  
Low Levels ◽  
Phosphatase And Tensin Homologue

The modulatory effect of miR-21 on the proliferation of melanoma cells through stimulation of PTEN (Phosphatase and tensin homologue deleted on chromosome 10) expression was investigated in the current study. PTEN, as a tumor suppressor, is expressed in low levels in melanoma tissues and cell lines. Nevertheless, miR-21 can stimulate cancer development and suppress cell apoptosis. Overexpression of PTEN substantially impaired the proliferation of miR-21-treated melanoma cells. In addition, miR-21 and PTEN were observed to exhibit a combinatorial effect, whereas miR-21 could negatively regulate the expression of PTEN. In conclusion, these findings demonstrate that miR-21 affects melanoma development by targeting PTEN, establishing a new strategy for treating malignant melanoma. Furthermore, in this study, microparticles and nanoparticles were employed as carriers to construct, through the self-assembly method, nanocapsules carrying miR-21 in order to develop an efficient nanocapsule delivery system of miR-21 against melanoma cells.

scholarly journals PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells

2019 ◽  
Vol 20 (18) ◽  
pp. 4631 ◽  
Author(s):  
Shunsuke Noguchi ◽  
Ryo Ogusu ◽  
Yusuke Wada ◽  
Satoshi Matsuyama ◽  
Takashi Mori
Keyword(s):  
Radiation Therapy ◽  
Luciferase Activity ◽  
Melanoma Cells ◽  
Expression Level ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Oral Melanoma ◽  
Luciferase Activity Assay ◽  
Oral Malignant Melanoma ◽  
Pre Treatment

Canine oral malignant melanoma (CoMM) is often treated by radiation therapy in veterinary medicine. However, not all cases are successfully managed by this treatment. For improved efficacy of radiation therapy, biomarkers predicting the radiosensitivity of melanoma cells need to be explored. Here, we, first, developed the radioresistant CoMM cell line, KMeC/R. We found that the expression level of phosphatase and tensin homolog (PTEN) of KMeC/R cells was significantly downregulated compared with KMeC cells. Overexpression of PTEN successfully restored the radiosensitivity of KMeC/R cells, and silencing of PTEN significantly increased the radioresistance of the CoMM cells tested. Next, we focused on microRNAs (miRNAs) to explore the mechanisms of downregulation of PTEN in KMeC/R cells. miR-374b was upregulated in KMeC/R cells compared with that in KMeC cells and in the irradiated CoMM cells tested. Furthermore, miR-374b directly targeted PTEN based on the luciferase activity assay. Moreover, the extrinsic miR-374b significantly increased the radioresistance of KMeC cells. In addition, the expression level of PTEN was significantly downregulated and that of miR-374b tended to be upregulated in recurrent CoMM tissues after radiation therapy compared with the pre-treatment tissues. Thus, the current study suggested that the miR-374b/PTEN signaling pathway possibly plays an important role in CoMM radiosensitivity.

scholarly journals Chamazulene-Rich Artemisia arborescens Essential Oils Affect the Cell Growth of Human Melanoma Cells

Plants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1000
Author(s):  
Alessandra Russo ◽  
Maurizio Bruno ◽  
Rosanna Avola ◽  
Venera Cardile ◽  
Daniela Rigano
Keyword(s):  
Essential Oils ◽  
Defense Mechanisms ◽  
Membrane Integrity ◽  
Melanoma Cells ◽  
Human Malignant Melanoma ◽  
Phosphatase And Tensin Homolog ◽  
Cell Membrane Integrity ◽  
Melanoma Cancer ◽  
Tensin Homolog ◽  
Ic50 Values

Artemisia arborescens is an aromatic shrub whose essential oils are considered a potential source of molecules with industrial and pharmaceutical interest. The chemical profile of A. arborescens essential oils (EOs) was shown to be quite variable and various chemotypes have been identified. In this study, we compared the EOs composition of A. arborescens leaves and flowers collected from four different locations in Sicily. The EOs were assayed for their antiproliferative activity against A375 human malignant melanoma cells, also testing cell viability and cell membrane integrity. The evaluation of DNA fragmentation and caspase-3 activity assay was employed for the detection of apoptosis. The expression of Bcl-2, Bax, cleaved caspase-9, PTEN (Phosphatase and tensin homolog), Hsp70 (Heat Shock Protein 70 kilodaltons) and SOD (superoxide dismutase) proteins was evaluated by Western blot analysis. The levels of ROS and GSH were also analyzed. Results show that EOs presented significant differences in their composition, yield, and cytotoxic activity depending on the collection site. The chamazulene/camphor-rich EOs from plants collected in Acqua Calda (Lipari) resulted particularly active on melanoma cancer cells (IC50 values of 6.7 and 4.5 µg/mL), being able to trigger apoptotic death probably interfering with endogenous defense mechanisms. These oils may be considered as a natural resource of chamazulene, containing this compound up to 63%.

scholarly journals Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 290 ◽  
Author(s):  
Yanlong Yin ◽  
Ben Hu ◽  
Xiao Yuan ◽  
Li Cai ◽  
Huile Gao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Delivery System ◽  
Self Assembly ◽  
Targeted Delivery ◽  
Polymer Network ◽  
Temperature Sensitive ◽  
Sustained Drug Release ◽  
Specific Chemical ◽  
Chemical Structures ◽  
Therapy Strategy

Nanogel-based nanoplatforms have become a tremendously promising system of drug delivery. Nanogels constructed by chemical crosslinking or physical self-assembly exhibit the ability to encapsulate hydrophilic or hydrophobic therapeutics, including but not limited to small-molecule compounds and proteins, DNA/RNA sequences, and even ultrasmall nanoparticles, within their 3D polymer network. The nanosized nature of the carriers endows them with a specific surface area and inner space, increasing the stability of loaded drugs and prolonging their circulation time. Reactions or the cleavage of chemical bonds in the structure of drug-loaded nanogels have been shown to trigger the controlled or sustained drug release. Through the design of specific chemical structures and different methods of production, nanogels can realize diverse responsiveness (temperature-sensitive, pH-sensitive and redox-sensitive), and enable the stimuli-responsive release of drugs in the microenvironments of various diseases. To improve therapeutic outcomes and increase the precision of therapy, nanogels can be modified by specific ligands to achieve active targeting and enhance the drug accumulation in disease sites. Moreover, the biomembrane-camouflaged nanogels exhibit additional intelligent targeted delivery features. Consequently, the targeted delivery of therapeutic agents, as well as the combinational therapy strategy, result in the improved efficacy of disease treatments, though the introduction of a multifunctional nanogel-based drug delivery system.

scholarly journals Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy

Oncotarget ◽  
2014 ◽  
Vol 5 (10) ◽  
pp. 3273-3286 ◽  
Author(s):  
Rachel Abbotts ◽  
Rosalyn Jewell ◽  
Jérémie Nsengimana ◽  
David J Maloney ◽  
Anton Simeonov ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Personalized Therapy ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

scholarly journals Self-Assembly of Soluble Chitosan Derivatives Nanoparticles for Vaccine: Synthesis, Characterization and Evaluation

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4097
Author(s):  
Jinbao Liu ◽  
Shuang Yu ◽  
Wanying Qu ◽  
Zheng Jin ◽  
Kai Zhao
Keyword(s):  
Ammonium Chloride ◽  
Self Assembly ◽  
Water Solubility ◽  
Degree Of Substitution ◽  
Synthesis Process ◽  
Assembly Method ◽  
Chitosan Nanoparticle ◽  
New Strategy ◽  
One Step ◽  
Acid Aqueous Solution

Herein, a novel chitosan derivative nanoparticle was proposed to function as a delivery carrier. First of all, an improvement was made to the way N-2-hydroxypropyl trimcthyl ammonium chloride chitosan (N-2-HACC) was synthesized. Moreover, the solution to one-step synthesis of N-2-HACC from chitosan (CS) was developed. Different from the previous report, the synthesis process was simplified, and there was a reduction in the amount of 2,3-epoxypropyl trimethyl ammonium chloride (EPTAC) used. With its excellent water solubility maintained, the relatively low degree of substitution was controlled to facilitate the cross-linking reaction. The results obtained from 1H-NMR, FTIR spectroscopy, and XRD indicated a smooth EPTAC onto CS for the formation of N-2-HACC with 59.33% the degree of substitution (DS). According to our results, N-2-HACC could be dissolved in various organic solvents, deionized water, 1% acetic acid aqueous solution, and others at room temperature. Finally, a novel chitosan nanoparticle material was prepared using the self-assembly method with β-glycerophosphate sodium (β-GC), with excellent immune properties achieved, thus providing a new strategy for chitosan self-assembled nanoparticles.

pH Dependent Release Potential of Natural Polymers in Sustained Release of Ornidazole From Colon Targeted Delivery System)

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul
Keyword(s):  
Drug Release ◽  
Delivery System ◽  
Targeted Delivery ◽  
Guar Gum ◽  
Acidic Environment ◽  
Natural Polymers ◽  
Weight Variation ◽  
Curve Determination ◽  
Preformulation Studies

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide

Targeted Delivery of siRNA Therapeutics using Ligand Mediated Biodegradable Polymeric Nanocarriers

2018 ◽  
Vol 24 (16) ◽  
pp. 1788-1800 ◽  
Author(s):  
Kye-Soo Cho ◽  
Seo-Jin Hong ◽  
Min-Hye Ahn ◽  
Sukdeb Pal ◽  
Pill-Hoon Choung ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Delivery System ◽  
Targeted Delivery ◽  
Sirna Delivery ◽  
Public Health Issue ◽  
Magic Bullet ◽  
Bodily Fluids ◽  
Low Cytotoxicity ◽  
Genetic And Environmental Factors ◽  
Sirna Delivery System

Background: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent “magic bullet” cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention. One of these promising and novel agents is the siRNA delivery system; however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA stability in the body’s circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA. Conclusion: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and 2) a description of the five major cancer-targeting ligands.

scholarly journals High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)

2020 ◽  
Vol 40 (8) ◽  
pp. 1854-1869
Author(s):  
Keith A. Strand ◽  
Sizhao Lu ◽  
Marie F. Mutryn ◽  
Linfeng Li ◽  
Qiong Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
High Throughput ◽  
Knockout Mice ◽  
Vascular Remodeling ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Protective Effects ◽  
High Throughput Screen ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

scholarly journals Photoacoustics for listening to Metal Nanoparticles Super-Aggregates

2021 ◽  
Author(s):  
Roberto Li Voti ◽  
Grigore Leahu ◽  
Concita Sibilia ◽  
Roberto Matassa ◽  
Giuseppe Familiari ◽  
...  
Keyword(s):  
Metal Nanoparticles ◽  
Size Distribution ◽  
Packing Density ◽  
Self Assembly ◽  
Détection Signal ◽  
Photoacoustic Detection ◽  
New Strategy ◽  
Aggregate Packing ◽  
Detection Signal

Photoacoustic detection signal has been used to build a new strategy to determine the mesoscale self-assembly of metal nanoparticles in terms of size distribution and aggregate packing density (metal nanoparticles...

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