Immuno Nanoparticles Integrated Electrical Control of Targeted Cancer Cell Development Using Whole Cell Bioelectronic Device

Hondroulis, Evangelia; Zhang, Rui; Zhang, Chengxiao; Chen, Chunying; Ino, Kosuke; Matsue, Tomokazu; Li, Chen Zhong

doi:10.7150/thno.8575

Cited by 28 publications

(16 citation statements)

References 44 publications

(39 reference statements)

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“…It could be a consequence of the response of V m to the alternating field. The sensitivity of the cancer cell membrane to electric field has been reported to be dependent on the frequency of the field (Hondroulis et al 2014 ), in a manner we find similar to the NPs’ size effect. In this paper, we show that the condition(s) characterizing the NPs’ size-dependent efficacy of EMF therapy of cancer cells can be derived from the parameters for the SPR-triggered electric field.…”

Section: Introductionsupporting

confidence: 84%

“…As a result, it would be inadequate for explaining the contributions or the roles of factors such as the NPs’ size, shape, metal type and their absorption characteristics to the thermal or electric field ( E int ) effects on the cancer cells. For example, some studies have tried to analyze the effect of externally applied AC electric fields on cancer cells, with the aim of determining optimal frequencies that can hinder cell proliferation (Schwab et al 2012 ; Hondroulis et al 2014 ). The potential effect of the external electric field on cancer cells has also been linked to the electrical properties of the cells, through the bioelectric interaction of the cytoplasm with the extracellular environment.…”

Section: Introductionmentioning

confidence: 99%

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Important parameters for optimized metal nanoparticles-aided electromagnetic field (EMF) effect on cancer

2018

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BackgroundA number of experimental research findings for the metal nanoparticles (NPs)-mediated EMF photothermal therapy of cancer cells show an intriguing trend of the NPs’ size-dependent efficacy. This is a phenomenon we find to trend with the light absorption bandwidth behavior (full width at half maximum) of the NPs and the accompanying electric field enhancement. We find that the nanoparticle sizes that have been reported to produce the optimized effect on cancer cells are of minimum absorption bandwidth and optimized electric field magnitude. While the death of cancer cells under the NPs-aided EMF effect has in the past attracted varied interpretations, either as a thermal or non-thermal effect, photothermal effect has gained a wide acceptance due to the exhibited hyperthermia. However, the exhibited trend of the NPs’ size-dependent efficacy is beginning to feature as a possible manifestation of other overlooked underlying or synergistic phenomenal conditions.MethodWe present a theoretical model and analysis which reveal that the contribution and efficacy of the metal NPs in the destruction of cancer depend partly but significantly on the accompanying electric field intensity enhancement factor and partly on their absorption cross-section.ResultsThis paper finds that, other than the expected hyperthermia, the metal NPs’ sizes for the optimized therapy on cancer cells seem to fulfill other synergistic conditions which need to come to the fore. We find interplay between electric field and thermal effects as independent energy channels where balancing may be important for the optimized EMF effect, in the ratio of about 5:1. The required balancing depends on the absorption bandwidth and absorption cross-section of the NPs, the frequency of EMF used and the relative permittivity of the cancer cells. The NPs’ size-dependent efficacy decreases away from the NPs’ size of minimum absorption bandwidth, which is around 20 nm for Au NPs or other shapes of equivalent surface area–volume ratio. While the absorption wavelength peak for metal NPs would change with the change of shape, the responsible condition(s) for optimizing the efficacy remains relatively invariable.ConclusionFrom the modeling and the analysis of the NPs’ size for optimizing the EMF therapy on cancer cells, the ratio of electric field enhancement by metal NPs to the associated thermal effect is a very important factor for efficacy.

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Section: Introductionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Important parameters for optimized metal nanoparticles-aided electromagnetic field (EMF) effect on cancer

2018

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“…We repeated the VTD experiments (0–300 μM) in non-cancerous kidney (HEK293) cells [ 46 ] ( Supplementary Figure S4H ), and we obtained similar results as those obtained in non-cancerous HUVEC cells ( Supplementary Figure S4G ). Both HUVEC and HEK-293 cells have been used extensively as control non-cancerous cells next to various cancer cell lines [ 47 , 48 ]. Together, these results suggest VTD needs higher doses to trigger cell death in normal cells with low levels of cytoplasmic mot-2 and stresses as previously described [ 2 ].…”

Section: Resultsmentioning

confidence: 99%

A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2

et al. 2015

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Veratridine (VTD), an alkaloid derived from the Liliaceae plant shows anti-tumor effects; however, its molecular targets have not been thoroughly studied. Using a high-throughput drug screen, we found that VTD enhances transactivation of UBXN2A, resulting in upregulation of UBXN2A in the cytoplasm, where UBXN2A binds and inhibits the oncoprotein mortalin-2 (mot-2). VTD-treated cancer cells undergo cell death in UBXN2A- and mot-2-dependent manners. The cytotoxic function of VTD is grade-dependent, and the combined treatment with a sub-optimal dose of the standard chemotherapy, 5-Fluorouracil (5-FU) and etoposide, demonstrated a synergistic effect, resulting in higher therapeutic efficacy. VTD influences the CD44+ stem cells, possibly through UBXN2A-dependent inhibition of mot-2. The VTD-dependent expression of UBXN2A is a potential candidate for designing novel strategies for colon cancer treatment because: 1) In 50% of colon cancer patients, UBXN2A protein levels in tumor tissues are significantly lower than those in the adjacent normal tissues. 2) Cytoplasmic expression of the mot-2 protein is very low in non-cancerous cells; thus, VTD can produce tumor-specific toxicity while normal cells remain intact. 3) Finally, VTD or its modified analogs offer a valuable adjuvant chemotherapy strategy to improve the efficacy of 5-FU-based chemotherapy for colon cancer patients harboring WT-p53.

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“…Other electro-stimulated systems that could prove promising for cancer applications include sensing electrodes in an alginate matrix 124 , electrical impedance sensing system 125 , iron-alginate thin-films 126 , electro-active hydrogel based polymer matrix 127 , 128 , gold nanoparticles activated by light and an electric field 129 , nanowire substrates 130 , and platinum microelectrodes 131 .…”

Section: Electro-thermally Triggered Theranosticsmentioning

confidence: 99%

Remotely Triggered Nano-Theranostics For Cancer Applications

Sneider¹,

VanDyke²,

Paliwal³

et al. 2017

Nanotheranostics

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Nanotechnology has enabled the development of smart theranostic platforms that can concurrently diagnose disease, start primary treatment, monitor response, and, if required, initiate secondary treatments. Recent in vivo experiments demonstrate the promise of using theranostics in the clinic. In this paper, we review the use of remotely triggered theranostic nanoparticles for cancer applications, focusing heavily on advances in the past five years. Remote triggering mechanisms covered include photodynamic, photothermal, phototriggered chemotherapeutic release, ultrasound, electro-thermal, magneto-thermal, X-ray, and radiofrequency therapies. Each section includes a brief overview of the triggering mechanism and summarizes the variety of nanoparticles employed in each method. Emphasis in each category is placed on nano-theranostics with in vivo success. Some of the nanotheranostic platforms highlighted include photoactivatable multi-inhibitor nanoliposomes, plasmonic nanobubbles, reduced graphene oxide-iron oxide nanoparticles, photoswitching nanoparticles, multispectral optoacoustic tomography using indocyanine green, low temperature sensitive liposomes, and receptor-targeted iron oxide nanoparticles loaded with gemcitabine. The studies reviewed here provide strong evidence that the field of nanotheranostics is rapidly evolving. Such nanoplatforms may soon enable unique advances in the clinical management of cancer. However, reproducibility in the synthesis procedures of such “smart” platforms that lend themselves to easy scale-up in their manufacturing, as well as the development of new and improved models of cancer that are more predictive of human responses, need to happen soon for this field to make a rapid clinical impact.

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Immuno Nanoparticles Integrated Electrical Control of Targeted Cancer Cell Development Using Whole Cell Bioelectronic Device

Cited by 28 publications

References 44 publications

Important parameters for optimized metal nanoparticles-aided electromagnetic field (EMF) effect on cancer

Important parameters for optimized metal nanoparticles-aided electromagnetic field (EMF) effect on cancer

A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2

Remotely Triggered Nano-Theranostics For Cancer Applications

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