Poly-γ-glutamic acid derived nanopolyplexes for up-regulation of gamma-glutamyl transpeptidase to augment tumor active targeting and enhance synergistic antitumor therapy by regulating intracellular redox homeostasis

2020 ◽  
Vol 8 (21) ◽  
pp. 5955-5968
Author(s):  
Fangying Yu ◽  
Yun Zhu ◽  
Yupeng Liu ◽  
Guoxi Qiu ◽  
Xuwei Shang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Glutamic Acid ◽  
Tumor Therapy ◽  
Redox Homeostasis ◽  
Drug Accumulation ◽  
Active Targeting ◽  
Gamma Glutamyl Transpeptidase ◽  
Antitumor Therapy ◽  
Glutamyl Transpeptidase ◽  
Targeting Strategy

The active targeting strategy has achieved inspiring progress for drug accumulation in tumor therapy; however, the insufficient expression level of many potential receptors poses challenges for drug delivery.

scholarly journals Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 650 ◽  
Author(s):  
Alfonsina Milito ◽  
Mariarita Brancaccio ◽  
Michael Lisurek ◽  
Mariorosario Masullo ◽  
Anna Palumbo ◽  
...  
Keyword(s):  
Redox Homeostasis ◽  
Glutathione Metabolism ◽  
Embryonic Cells ◽  
Gamma Glutamyl Transpeptidase ◽  
Docking Analysis ◽  
Gamma Glutamyl ◽  
A Cell ◽  
Human Use ◽  
Further Development ◽  
Glutamyl Transpeptidase

Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT inhibitors that have been evaluated in clinical trials are too toxic for human use. We have previously identified ovothiols, 5(Nπ)-methyl-thiohistidines of marine origin, as non-competitive-like inhibitors of GGT that are more potent than the known GGT inhibitor, 6-diazo-5-oxo-l-norleucine (DON), and are not toxic for human embryonic cells. We extended these studies to the desmethylated form of ovothiol, 5-thiohistidine, and confirmed that this ovothiol derivative also acts as a non-competitive-like GGT inhibitor, with a potency comparable to ovothiol. We also found that both 5-thiohistidine derivatives act as reversible GGT inhibitors compared to the irreversible DON. Finally, we probed the interactions of 5-thiohistidines with GGT by docking analysis and compared them with the 2-thiohistidine ergothioneine, the physiological substrate glutathione, and the DON inhibitor. Overall, our results provide new insight for further development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors.

Hierarchically stimuli-responsive nanovectors for improved tumor penetration and programed tumor therapy

Nanoscale ◽  
2018 ◽  
Vol 10 (28) ◽  
pp. 13737-13750 ◽  
Author(s):  
Junjie Liu ◽  
Xingming Guo ◽  
Zhong Luo ◽  
Jixi Zhang ◽  
Menghuan Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Solid Tumors ◽  
Tumor Therapy ◽  
Stimuli Responsive ◽  
Antitumor Therapy ◽  
Tumor Penetration

Poor drug delivery to solid tumors remains a great challenge for effective antitumor therapy.

scholarly journals Active Targeting Gold Nanoparticle for Chemotherapy Drug Delivery: A Review

2021 ◽  
Author(s):  
Azhoma Gumala ◽  
Sutriyo Sutriyo
Keyword(s):  
Drug Delivery ◽  
Active Targeting ◽  
Tumour Site ◽  
Chemotherapy Drug ◽  
Therapeutic Outcomes ◽  
Normal Site ◽  
Specific Cancer ◽  
Targeting Strategy

Objective Active targeting strategy in chemotherapy drug delivery aims to improve the therapeutic outcomes and minimise the side effects of chemotherapeutics. This review discusses utilising ligands attached to gold nanoparticles (AuNPs) along with several specific ligands attached to AuNPs for active targeting in chemotherapy drug delivery. Key finding Antibodies, peptides, vitamins, DNA, polysaccharides, aptamers, and hormones showed active-targeting abilities as ligands attached to AuNPs. Active-targeting AuNPs enhanced cellular uptake and cytotoxicity in a specific cancer cell in vitro while reducing tumor growth in vivo by improving the photothermal, photodynamic and chemotherapy effects. Active-targeting ligands increased the internalization of AuNPs loaded onto the specific tumour site and minimised the accumulation in the normal site. Conclusion AuNPs with active-targeting ligands such as antibodies, peptides, vitamins, DNA polysaccharides, aptamers, and hormones can improve the therapeutic outcomes of chemotherapeutics and can attenuate the toxicity effect in normal cells. For further research and development, researchers should be addressing AuNP characterization, drug–ligand disposition, active-targeting AuNP quantification, and target-AuNPs pertinence concerning the desired therapeutic outcomes.

Relationship Between Gamma-glutamyl Transpeptidase Activity and Inflammatory Response in Lichen Planus

2018 ◽  
Vol 69 (3) ◽  
pp. 739-743 ◽  
Author(s):  
Madalina Irina Mitran ◽  
Ilinca Nicolae ◽  
Corina Daniela Ene ◽  
Cristina Iulia Mitran ◽  
Clara Matei ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lichen Planus ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Functional Adaptation ◽  
Physical Factors ◽  
Inflammatory Disorder ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Glutamyl Transpeptidase

Chemicals used in the manufacture of synthetic fibers have been associated with undesirable side effects such as itching or skin lesions and it seems that they are involved in the induction of pathological processes such as oxidative stress and inflammation. Lichen planus (LP) can be regarded as an inflammatory disorder, chemical and physical factors playing an important role in the perpetuation of the inflammatory process. Gamma-glutamyl transpeptidase (GGT) plays an important role in the preservation of skin architecture and modulation of skin inflammation. In this study, we found that GGT activity is increased in LP patients with mild inflammation, whilst GGT is inactivated under conditions of severe inflammation. Therefore, GGT is involved in the inflammatory process, but there is no a positive correlation between its activity and the intensity of the inflammatory response. This functional adaptation of the enzyme may be due to down-regulation of its synthesis under free radical overload conditions. Understanding the molecular mechanisms involved in the modulation of intracellular redox homeostasis is an important step in the pharmacological management of patients with LP.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy

2017 ◽  
Vol 23 (3) ◽  
pp. 454-466 ◽  
Author(s):  
Daniele R. Nogueira-Librelotto ◽  
Cristiane F. Codevilla ◽  
Ammad Farooqi ◽  
Clarice M. B. Rolim
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Therapeutic Benefit ◽  
Active Targeting ◽  
Future Research ◽  
Passive Targeting ◽  
The Right ◽  
Review Current ◽  
Target Effects

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research.

Hypoxia Responsive Drug Delivery Systems in Tumor Therapy

2016 ◽  
Vol 22 (19) ◽  
pp. 2808-2820 ◽  
Author(s):  
Houman Alimoradi ◽  
Siddharth S. Matikonda ◽  
Allan B. Gamble ◽  
Gregory I. Giles ◽  
Khaled Greish
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Tumor Therapy ◽  
Delivery Systems
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