Choline Phosphate Lipid Insert and Rigidify Cell Membrane for Targeted Cancer Chemo-immunotherapy

2021 ◽  
Author(s):  
Shengran Li ◽  
Weikang Mei ◽  
Xiaozhen Wang ◽  
Sangni Jiang ◽  
Xinxin Yan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Phosphatidyl Choline ◽  
Choline Phosphate

To prevent tumor reproduction and metastasis, a method to modify the membrane of cancer cells was designed to suppress their vitality. We synthesized a phosphatidyl choline reversed choline phosphate lipid...

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

2020 ◽  
Vol 20 ◽  
Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Quantum Chemical ◽  
Density Functional ◽  
Enzyme Regulation ◽  
Amide Derivatives ◽  
Pass Through ◽  
Hydrolysis Of ◽  
Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

scholarly journals A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jianmin Xiao ◽  
Miao Yan ◽  
Ke Zhou ◽  
Hui Chen ◽  
Zhaowei Xu ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
High Yield ◽  
Ros Generation ◽  
Superoxide Dismutase 1 ◽  
Nuclear Targeting ◽  
Dual Mode ◽  
Red Cell Membrane ◽  
Cancer Cell Death ◽  
Drug Nanocarriers

Abstract The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Enhancement of radiotherapeutic efficacy for esophageal cancer by paclitaxel-loaded red blood cell membrane nanoparticles modified by the recombinant protein anti-EGFR-iRGD

2018 ◽  
Vol 33 (5) ◽  
pp. 707-724 ◽  
Author(s):  
Wei Ren ◽  
Huizi Sha ◽  
Jing Yan ◽  
Puyuan Wu ◽  
Ju Yang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cell Membrane ◽  
Recombinant Protein ◽  
Blood Cell ◽  
Cancer Cells ◽  
Red Blood Cell ◽  
Enhancement Ratio ◽  
Red Blood Cell Membrane ◽  
Egfr Expression ◽  
Esophageal Cancer Cells

Paclitaxel is widely used as a radiosensitizer for various tumors, including esophageal cancer, but its therapeutic effect remains to be improved. In this study, we constructed a novel nano-radiosensitizer, anti-EGFR-iRGD-conjugated (iE)-PRNPs, by conjugating the recombinant protein anti-epidermal growth factor receptor (EGFR)-internalizing arginine-glycine-aspartic (iRGD) to the surface of paclitaxel-loaded red blood cell membrane nanoparticles (PRNPs). The iE-PRNPs were confirmed to possess tumor-targeting, high penetrability, and sustained release properties that free paclitaxel does not possess. Compared with that of paclitaxel, the sensitizer enhancement ratio of iE-PRNPs was significantly increased (1.32-fold and 1.25-fold) in esophageal cancer cells with high and low expression levels of EGFR, respectively. Additionally, compared with that of unmodified PRNPs, the sensitizer enhancement ratio of iE-PRNPs in EGFR-overexpressing esophageal cancer cells was significantly increased (1.27-fold), while that of PRNPs in esophageal cancer cells with a low EGFR expression level increased slightly (1.06-fold). The improved radiosensitization effect was associated with enhanced G2/M arrest, increased reactive oxygen species, and more effective induction of DNA double-strand breaks. In summary, iE-PRNPs appear to be a novel type of radiosensitizer with the potential to overcome the bottleneck of esophageal cancer radiotherapeutic efficacy.

The metastasis suppressor, NDRG1, attenuates oncogenic TGF-β and NF-κB signaling to enhance membrane E-cadherin expression in pancreatic cancer cells

2018 ◽  
Vol 40 (6) ◽  
pp. 805-818 ◽  
Author(s):  
Sharleen V Menezes ◽  
Leyla Fouani ◽  
Michael L H Huang ◽  
Bekesho Geleta ◽  
Sanaz Maleki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Metastasis Suppressor ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
E Cadherin

AbstractThe metastasis suppressor, N-myc downstream-regulated gene-1 (NDRG1), plays multifaceted roles in inhibiting oncogenic signaling and can suppress the epithelial mesenchymal transition (EMT), a key step in metastasis. In this investigation, NDRG1 inhibited the oncogenic effects of transforming growth factor-β (TGF-β) in PANC-1 pancreatic cancer cells, promoting expression and co-localization of E-cadherin and β-catenin at the cell membrane. A similar effect of NDRG1 at supporting E-cadherin and β-catenin co-localization at the cell membrane was also demonstrated for HT-29 colon and CFPAC-1 pancreatic cancer cells. The increase in E-cadherin in PANC-1 cells in response to NDRG1 was mediated by the reduction of three transcriptional repressors of E-cadherin, namely SNAIL, SLUG and ZEB1. To dissect the mechanisms how NDRG1 inhibits nuclear SNAIL, SLUG and ZEB1, we assessed involvement of the nuclear factor-κB (NF-κB) pathway, as its aberrant activation contributes to the EMT. Interestingly, NDRG1 comprehensively inhibited oncogenic NF-κB signaling at multiple sites in this pathway, suppressing NEMO, Iĸĸα and IĸBα expression, as well as reducing the activating phosphorylation of Iĸĸα/β and IĸBα. NDRG1 also reduced the levels, nuclear co-localization and DNA-binding activity of NF-κB p65. Further, Iĸĸα, which integrates NF-κB and TGF-β signaling to upregulate ZEB1, SNAIL and SLUG, was identified as an NDRG1 target. Considering this, therapies targeting NDRG1 could be a new strategy to inhibit metastasis, and as such, we examined novel anticancer agents, namely di-2-pyridylketone thiosemicarbazones, which upregulate NDRG1. These agents downregulated SNAIL, SLUG and ZEB1 in vitro and in vivo using a PANC-1 tumor xenograft model, demonstrating their marked potential.

scholarly journals Cell Membrane Proteomic Analysis Identifies Proteins Differentially Expressed in Osteotropic Human Breast Cancer Cells

Neoplasia ◽  
2008 ◽  
Vol 10 (9) ◽  
pp. 1014-IN11 ◽  
Author(s):  
Philippe Kischel ◽  
François Guillonneau ◽  
Bruno Dumont ◽  
Akeila Bellahcène ◽  
Verena Stresing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Proteomic Analysis ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Differentially Expressed ◽  
Human Breast Cancer Cells ◽  
Human Breast

The association of an exosomal form of PD-L1 with immunosuppressive activity and gastric cancer prognosis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 47-47
Author(s):  
Yibo Fan ◽  
Xiaofang Che ◽  
Zhi Li ◽  
Xiujuan Qu ◽  
Yunpeng Liu
Keyword(s):  
Gastric Cancer ◽  
Cell Membrane ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Gastric Cancer Cell ◽  
Tumor Cell Membrane ◽  
Gastric Cancer Cell Lines ◽  
Gastric Cancer Patients

47 Background: The greatest challenge in cancer immunotherapy is to identify efficient predictive biomarkers to select patients for treatment. Though tumor cell membrane PD-L1 has been most anticipated, tumor cell membrane PD-L1 does not correlate with higher response rates and predict for clinical benefit. Subsequently studies showed that the prognostic value of tumor cell membrane PD-L1 in cancer patients remains controversial. In addition to membrane-associated PD-L1, tumor cell also secreted extracellular soluble PD-L1 in the microenvironment. However, even if extracellular soluble PD-L1 was detected, it did not solve the problem mentioned above. In the present study, we discovered another form of PD-L1 in extracellular microenvironment in cancer cells, that is exosomal PD-L1. However, the predictive role and the effect of tumor-derived exosomal PD-L1 is unclear. Methods: We evaluated the prognostic value of exosomal PD-L1 in the plasma of gastric cancer patients by ELISA and the effect of exosomal PD-L1-derived from gastric cancer cell lines by Western blot and Flow cytometry analysis. Results: Exosomal PD-L1 was detected in plasma samples from 69 gastric cancer patients, and exosomal PD-L1 content was significantly associated with T stage (P = 0.012). Overall Survival was significantly lower in the high exosomal PD-L1 group (p = 0.021). Additionally, gastric cancer cells also secreted exosomal PD-L1, with the amounts positively associated with PD-L1 amounts in the corresponding gastric cancer cell lines. Besides, exosomal PD-L1 was more stable and showed stronger immunosuppressive effects in the microenvironment compared with soluble PD-L1. Conclusions: Exosomal PD-L1 might predict the survival in gastric cancer, and induces higher T-cell apoptosis levels compared with soluble PD-L1.

An Autonomous Cell Type Selective Irreversible Electroporation Microsystem Using Insulator Based Dielectrophoresis (IDEP)

2008 ◽  
Author(s):  
Hadi Shafiee ◽  
Rafael V. Davalos
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Electric Field ◽  
Cancer Cells ◽  
Irreversible Electroporation ◽  
Cell Type ◽  
Electrode Arrays ◽  
Normal Cells ◽  
Dc Offset ◽  
Ac Field

Irreversible electroporation (IRE) is a method to kill cells by exposing the cell to intense electric field pulses[1]. It is postulated that the lipid bilayer rearranges to create permanent defects in the cell membrane which eventually leads to cell death via necrosis[1]. We postulate that the recurrence of cancer for patients treated for the disease would be minimized if their blood was monitored using a microdevice which would destroy existing or new exfoliated cancer cells. Dielectrophoresis (DEP) is the motion of polarizable particles that are suspended in an electrolyte when subjected to a spatially nonuniform electric field [2]. Insulator-based DEP uses insulating structures rather than electrode arrays to produce the nonuniform fields needed to drive DEP. We hypothesize that iDEP can enable the selective IRE of a particular cell type within a microfluidic platform. This manuscript demonstrates through modeling the feasibility of coupling iDEP with IRE using an AC field with a DC offset. Such a platform could be used to selectively destroy isolate cancer cells while not affecting normal cells.

scholarly journals Antitumor Effect of IL-2 and TRAIL Proteins Expressed by Recombinant Salmonella in Murine Bladder Cancer Cells

2021 ◽  
Vol 55 (4) ◽  
pp. 460-476
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cell Membrane ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Morphology ◽  
Antitumor Effect ◽  
Interleukin 2 ◽  
Continuous Increase ◽  
Bladder Cancer Cells

Background/Aims: Cancer is the second most deadly disease in the world. The bladder cancer is one of the most aggressive types and shows a continuous increase in the number of cases. The use of bacteria as live vectors to deliver molecules directly to the tumor is a promising tool and has been used as an adjuvant treatment against several types of cancer. The aim of this study was to investigate the antitumor effect of Interleukin 2 (IL-2), TNF-related apoptosis-inducing ligand (TRAIL) and protein MIX against murine bladder cancer cells, lineage MB49. Methods: The attenuated Salmonella strain SL3261 was transformed by inserting the IL-2 and TRAIL genes. The effects of proteins on cell viability (MTT method), cell morphology (optical microscopy), cell recovery (clonogenic assay), cell membrane (lactate dehydrogenase release - LDH), on oxidative stress pathway (levels of nitric oxide, NO) and apoptosis (flow cytometry and high resolution epifluorescence images) were evaluated at intervals of 24 and 48 hours of action. Results: The results showed that there was a decrease in cell viability via damage to the cell membrane, alteration of cell morphology, non-recovery of cells, increase in the production of NO and incubate for of cells in the state of apoptosis in the two periods analyzed. Conclusion: The data presented suggest that IL-2, TRAIL and their MIX proteins in MB49 cells have cytotoxic potential and that this is associated with oxidative stress and apoptosis pathways. These results may contribute to the development of new therapeutic strategies for bladder cancer.

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