Enzyme and Cancer Cell Selectivity of Nanoparticles: Inhibition of 3-D Metastatic Phenotype and Experimental Melanoma by Zinc Oxide

Delong, Robert K.; Mitchell, Jennifer A.; Morris, Robert T.; Comer, Jeffrey; Hurst, Miranda N; Ghosh, Kartik; Wanekaya, Adam K.; Mudge, Miranda C.; Schaeffer, Ashley; Washington, Laurie; Risor-Marhanka, Azure; Thomas, Spencer; Marroquin, Shanna; Lekey, Amber; Smith, Joshua; Garrad, Richard C.; Aryal, Santosh; Abdelhakiem, Mohamed; Glaspell, Garry

doi:10.1166/jbn.2017.2336

Cited by 14 publications

(18 citation statements)

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“…Nanoscale ZnO (<100 nm) and MgO (<50 nm), poly inosinic:poly cytidilic acid (poly I:C), torula yeast RNA and DNase were obtained from Sigma-Aldrich (St. Louis, MO, USA). The nanoparticle size and zeta potential were confirmed on a Malvern Zetananosizer (Westborough, MA, USA) as per our previous reports [ 4 , 8 , 9 ]. The NP were washed with double-distilled water (ddH 2 O) and precipitated from alcohol and air-dried to a powder within a biological safety cabinet prior to use.…”

Section: Methodsmentioning

confidence: 72%

“…In nanomedicine, the specific anticancer activity of zinc oxide (ZnO) nanoparticle (NP) is believed to be due to its reactive oxygen species (ROS) generation and tumor pH-dependent ion disassociation as well as the inhibition of various kinases important in cancer cell signaling [ 1 , 2 , 3 , 4 ]. Poly inosinic:poly cytidilic acid (poly I:C) is among the most well-characterized anticancer RNA, possessing RNA targeting and anti-metastatic activity [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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ZnO Nanoparticles Protect RNA from Degradation Better than DNA

et al. 2017

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Gene therapy and RNA delivery require a nanoparticle (NP) to stabilize these nucleic acids when administered in vivo. The presence of degradative hydrolytic enzymes within these environments limits the nucleic acids’ pharmacologic activity. This study compared the effects of nanoscale ZnO and MgO in the protection afforded to DNA and RNA from degradation by DNase, serum or tumor homogenate. For double-stranded plasmid DNA degradation by DNase, our results suggest that the presence of MgO NP can protect DNA from DNase digestion at an elevated temperature (65 °C), a biochemical activity not present in ZnO NP-containing samples at any temperature. In this case, intact DNA was remarkably present for MgO NP after ethidium bromide staining and agarose gel electrophoresis where these same stained DNA bands were notably absent for ZnO NP. Anticancer RNA, polyinosinic-polycytidylic acid (poly I:C) is now considered an anti-metastatic RNA targeting agent and as such there is great interest in its delivery by NP. For it to function, the NP must protect it from degradation in serum and the tumor environment. Surprisingly, ZnO NP protected the RNA from degradation in either serum-containing media or melanoma tumor homogenate after gel electrophoretic analysis, whereas the band was much more diminished in the presence of MgO. For both MgO and ZnO NP, buffer-dependent rescue from degradation occurred. These data suggest a fundamental difference in the ability of MgO and ZnO NP to stabilize nucleic acids with implications for DNA and RNA delivery and therapy.

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Section: Methodsmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

ZnO Nanoparticles Protect RNA from Degradation Better than DNA

et al. 2017

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“…The suppression of the fluorescence with RBD present at equimolar concentrations of NP suggests interaction. Stern-Volmer equation was applied to calculate the dissociation constant and the number of binding sites as we have previous described for ZnO NP (12). These data are shown in Table 2 below.…”

Section: Plos Onementioning

confidence: 99%

“…Its unique surface chemistry allows formation of ZnOH+ species which likely underlies its interaction to anionic membrane of cancer cells and its drug delivery activity [10,11]. Recent work from our research group suggests ZnO NP inhibition of experimental melanoma [12] can be improved by its interaction to poly I:C RNA [13].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Ras Binding Domain (RBD) by chemotherapeutic zinc oxide nanoparticles: Progress towards RAS pathway protein interference

et al. 2020

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Zinc oxide (ZnO) NP is considered as a nanoscale chemotherapeutic. Thus, the drug delivery of this inorganic NP is of considerable importance. Ras mutations are common in cancer and the activation of this signaling pathway is a hallmark in carcinoma, melanoma and many other aggressive malignancies. Thus, here we examined the binding and delivery of Ras binding domain (RBD), a model cancer-relevant protein and effector of Ras by ZnO NP. Shifts in zeta potential in water, PBS, DMEM and DMEM supplemented with FBS supported NP interaction to RBD. Fluorescence quenching of the NP was concentration-dependent for RBD, Stern–Volmer analysis of this data was used to estimate binding strength which was significant for ZnO-RBD (Kd < 10−5). ZnO NP interaction to RBD was further confirmed by pull-down assay demonstrated by SDS-PAGE analysis. The ability of ZnO NP to inhibit 3-D tumor spheroid was demonstrated in HeLa cell spheroids—the ZnO NP breaking apart these structures revealing a significant (>50%) zone of killing as shown by light and fluorescence microscopy after intra-vital staining. ZnO 100 nm was superior to ZnO 14 nm in terms of anticancer activity. When bound to ZnO NP, the anticancer activity of RBD was enhanced. These data indicate the potential diagnostic application or therapeutic activity of RBD-NP complexes in vivo which demands further investigation.

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“…For instance Hassan et al [161] found out that ZnONPs considerably declined elevated levels of oxidative stress markers and hepatocyte integrity, and also reduced high levels of serum of tumor alpha-l-fucosidase and markers alphafetoprotein when used against hepatocellular carcinoma HepG2, non-small cell lung cancer A549, and human prostate PC3. Also, DeLong et al [162] reported the efficacy of ZnONPs in inhibiting ERK enzyme and other cancerassociated kinases such as AKT, p70S6 K and CREB. ZnONPs has also been reported as an anticancer agent against human colon carcinoma LoVo, and HeLa among others [163,164].…”

Section: Applications Of Metallic Nanoparticles As Anticancer Agentsmentioning

confidence: 99%

Biomedical Applications of Green Synthesized-Metallic Nanoparticles: A Review

Lateef

Elegbede

Akinola

et al. 2019

PAJOLS

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Advances in the field of nanoscience and nanotechnology to modulate materials at nanoscale level has continued to have great impact on different disciplines of science and engineering as well as agriculture and medical fields. The surge in the utilization of benign and non-toxic biomolecules to engineer enhanced biocompatible nanomaterials has contributed to a large extent to the applications of nanomaterials in healthcare; an emerging sub-discipline termed nanomedicine. Among the several nanomaterials that have been produced, metallic nanoparticles occupy prime position owing to their optical, catalytic and biological characteristics. These nanoparticles, which are of different types existing singly as mono-metallic nanoparticles or in two or more metals as alloys have found extremely useful applications as antimicrobial, antioxidant, anticancer, antidiabetic, anticoagulant and thrombolytic agents amongst others. In this review, an attempt is made to project the different applications of green synthesized metallic nanoparticles in diverse areas of biomedicine, including the discussion of issues of toxicity and prospects of nanotechnology in biomedical field.

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Enzyme and Cancer Cell Selectivity of Nanoparticles: Inhibition of 3-D Metastatic Phenotype and Experimental Melanoma by Zinc Oxide

Cited by 14 publications

References 0 publications

ZnO Nanoparticles Protect RNA from Degradation Better than DNA

ZnO Nanoparticles Protect RNA from Degradation Better than DNA

Interaction of Ras Binding Domain (RBD) by chemotherapeutic zinc oxide nanoparticles: Progress towards RAS pathway protein interference

Biomedical Applications of Green Synthesized-Metallic Nanoparticles: A Review

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