Metal Oxide Nanoparticles as Versatile Therapeutic Agents Modulating Cell Signaling Pathways: Linking Nanotechnology with Molecular Medicine

Augustine, Robin; Mathew, Ansuja Pulickal; Sosnik, Alejandro

doi:10.1016/j.apmt.2017.01.010

Cited by 71 publications

(40 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Impairment of these pathways due to zinc deficiency may lead to loss of critical cellular functions and promotion of pro-oncogenic processes 36 . A previous study showed that ZnO nanoparticles lead to increased p53 protein levels and induction of apoptosis in HepG2 cells 37 . Another study showed decreased VEGFR expression, decreased tubule formation, and increased apoptosis in endothelial colony-forming cells as a result of ZnO treatment 38 .…”

Section: Discussionmentioning

confidence: 95%

Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

et al. 2019

View full text Add to dashboard Cite

Zinc is vital for the structure and function of~3000 human proteins and hence plays key physiological roles. Consequently, impaired zinc homeostasis is associated with various human diseases including cancer. Intracellular zinc levels are tightly regulated by two families of zinc transporters: ZIPs and ZnTs; ZIPs import zinc into the cytosol from the extracellular milieu, or from the lumen of organelles into the cytoplasm. In contrast, the vast majority of ZnTs compartmentalize zinc within organelles, whereas the ubiquitously expressed ZnT1 is the sole zinc exporter. Herein, we explored the hypothesis that qualitative and quantitative alterations in ZnT1 activity impair cellular zinc homeostasis in cancer. Towards this end, we first used bioinformatics to analyze inactivating mutations in ZIPs and ZNTs, catalogued in the COSMIC and gnomAD databases, representing tumor specimens and healthy population controls, respectively. ZnT1, ZnT10, ZIP8, and ZIP10 showed extremely high rates of loss of function mutations in cancer as compared to healthy controls. Analysis of the putative functional impact of missense mutations in ZnT1-ZnT10 and ZIP1-ZIP14, using homologous protein alignment and structural predictions, revealed that ZnT1 displays a markedly increased frequency of predicted functionally deleterious mutations in malignant tumors, as compared to a healthy population. Furthermore, examination of ZnT1 expression in 30 cancer types in the TCGA database revealed five tumor types with significant ZnT1 overexpression, which predicted dismal prognosis for cancer patient survival. Novel functional zinc transport assays, which allowed for the indirect measurement of cytosolic zinc levels, established that wild type ZnT1 overexpression results in low intracellular zinc levels. In contrast, overexpression of predicted deleterious ZnT1 missense mutations did not reduce intracellular zinc levels, validating eight missense mutations as loss of function (LoF) mutations. Thus, alterations in ZnT1 expression and LoF mutations in ZnT1 provide a molecular mechanism for impaired zinc homeostasis in cancer formation and/or progression.

show abstract

Section: Discussionmentioning

confidence: 95%

Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Inorganic nanoparticles, especially metal oxide nanoparticles (MONPs), are also studied for the speedy recovery of wounds. MONPs like zinc oxide (ZnO), titanium dioxide (TiO 2 ) and silicon dioxide (SiO 2 ) play important roles in the production of reactive oxygen species, which stimulate the proliferation of fibroblasts and wound healing [109].…”

Section: Nanoparticlesmentioning

confidence: 99%

Evolution of Nanotechnology in Delivering Drugs to Eyes, Skin and Wounds via Topical Route

et al. 2020

View full text Add to dashboard Cite

The topical route is the most preferred one for administering drugs to eyes, skin and wounds for reaching enhanced efficacy and to improve patient compliance. Topical administration of drugs via conventional dosage forms such as solutions, creams and so forth to the eyes is associated with very low bioavailability (less than 5%) and hence, we cannot rely on these for delivering drugs to eyes more efficiently. An intravitreal injection is another popular drug delivery regime but is associated with complications like intravitreal hemorrhage, retinal detachment, endophthalmitis, and cataracts. The skin has a complex structure that serves as numerous physiological barriers to the entry of exogenous substances. Drug localization is an important aspect of some dermal diseases and requires directed delivery of the active substance to the diseased cells, which is challenging with current approaches. Existing therapies used for wound healing are costly, and they involve long-lasting treatments with 70% chance of recurrence of ulcers. Nanotechnology is a novel and highly potential technology for designing formulations that would improve the efficiency of delivering drugs via the topical route. This review involves a discussion about how nanotechnology-driven drug delivery systems have evolved, and their potential in overcoming the natural barriers for delivering drugs to eyes, skin and wounds.

show abstract

“…One of the most novel properties of metal oxide and metallic nanoparticle is the ability to generate reactive oxygen species in either the presence or absence of irradiation. This property is mainly exploited in nanomedicine in the form of drug delivery of chemotherapeutic drugs [3][4][5].…”

Section: Introduction Nanomaterialsmentioning

confidence: 99%

“…Zinc oxide nanoparticles have been extensively studied. Nano zinc has shown the ability to selectively kill tumor cells [3,6]. Other applications of zinc oxide nanoparticles include bioimaging, gene delivery, biosensing, drug delivery.…”

Section: Introduction Nanomaterialsmentioning

confidence: 99%

Induction and evaluation of inflammatory markers by zinc oxide nanoparticles: A comparative study using in vitro and in vivo approaches.

Parvathi¹,

Boominathan²,

SridharKumar³

et al. 2019

biomedicalresearch

View full text Add to dashboard Cite

Zinc oxide nanoparticle is one of the most researched types of metal oxide nanoparticles in recent literature. Due to its unique properties such as biodegradability and reduced toxicity compared to other types of metallic nanoparticles, the application of zinc oxide nanoparticles has been increased in recent years. Most notable application is in the field of nanomedicine. Due to its ability to selectively kill cancer cells, zinc oxide nanoparticle has been used as a drug carrier for many chemotherapeutic drugs. The In vitro and in vivo models help us to understand the mechanism and the amount of toxicity induced by these nanoparticles in the immune system of humans. This can help in the formulation of personalized chemotherapeutic drugs. In this study, we analysed three differently synthesized zinc oxide nanoparticles (chemical precipitation, green chemistry approach, commercially available) on in vitro (human peripheral blood) and in vivo (Zebrafish) models. Pre-defined concentrations nanoparticles (5 µg/ml, 10 µg/ml, 15 µg/ml, 20 µg/ml, 25 µg/ml and 30 µg/ml) were used to analyse the amount of toxicity induced by zinc oxide nanoparticles. There was a dose dependent toxicity increase with in vitro and in vivo models after addition of zinc oxide nanoparticles. Commercially available zinc oxide nanoparticles showed highest toxicity and nanoparticles synthesized by green chemistry method showed lowest toxicity on comparison.

show abstract

Metal Oxide Nanoparticles as Versatile Therapeutic Agents Modulating Cell Signaling Pathways: Linking Nanotechnology with Molecular Medicine

Cited by 71 publications

References 138 publications

Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

Evolution of Nanotechnology in Delivering Drugs to Eyes, Skin and Wounds via Topical Route

Induction and evaluation of inflammatory markers by zinc oxide nanoparticles: A comparative study using in vitro and in vivo approaches.

Contact Info

Product

Resources

About