Nano-Enabled Delivery of Intracellular Therapeutics

Ostadhossein, Fatemeh; Daza, Enrique; Frankowski, Daniel; Goatz, Drew; Imgruet, Molly; Kus, Joseph; Lake, Ryan J.; Modak, Mallika; Olsen, Nick; Schwartz-Duval, Aaron S.; Zimmer, Alyssa; Kolmodin, Nicholas J.; Pan, Dipanjan

doi:10.1007/7355_2015_97

Cited by 3 publications

(4 citation statements)

References 70 publications

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“…Furthermore, the nanoparticles’ decoration with CB6 further elevated the potency of the drug which can be attributed to the facile internalization and translocation inside the cell, sustained release of the drug and enhanced bioavailability of the drug due to its solubilization in CB6 CNP Nic sample. [41] By far, solubility is regarded as the most important parameter to achieve desired concentration of drug at the site of the action for intended pharmacological response. The inadequate dissolution rate of the drug is also the limiting factor in the bioavailability of poorly water soluble compounds.…”

Section: Resultsmentioning

confidence: 99%

Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer

Ostadhossein

Misra

Mukherjee

et al. 2016

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Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host–guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host–guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host–guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition.

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Section: Resultsmentioning

confidence: 99%

Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer

Ostadhossein

Misra

Mukherjee

et al. 2016

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“…Very recently, Feng et al reported on the synthesis of charge convertible pH responsive CNP carrier with the capability of being imaged by strong fluorescent signal of CNP. The nanoparticles release payload based on the reduction of pH in the tumor microenvironment compared to the healthy cells, a principle known as Warburg effect . The pH responsiveness of the nanoparticles originated from the coating applied on the CNP core.…”

Section: Cds In Drug and Gene Deliverymentioning

confidence: 99%

“…The nanoparticles release payload based on the reduction of pH in the tumor microenvironment compared to the healthy cells, a principle known as Warburg effect. 67 The pH responsiveness of the nanoparticles originated from the coating applied on the CNP core. The CNP core was covalently conjugated to a model drug (cisplatin prodrug) through NHS/EDC chemistry.…”

Section: Cds In Drug and Gene Deliverymentioning

confidence: 99%

Functional carbon nanodots for multiscale imaging and therapy

Ostadhossein

Pan

2016

WIREs Nanomed Nanobiotechnol

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As an emerging class of carbon nanomaterials, carbon dots (CDs) have garnered many researchers' interests in the past decade due to their excellent biocompatibility, replete surface functional groups, water dispersibility, and unique photoluminescence. These extraordinary properties have opened new avenues for their advanced application in cell labeling, bioimaging, drug delivery, sensors, and energy-related devices. In this paper, we critically review recent advances in the synthetic strategies and the application of CDs for biological purposes, specifically, imaging and therapy. Finally, a perspective has been given on the potential challenges facing the translation of these materials from the bench to the market. WIREs Nanomed Nanobiotechnol 2017, 9:e1436. doi: 10.1002/wnan.1436 For further resources related to this article, please visit the WIREs website.

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“…Due to its high water solubility (1865 g/L at 20 °C) the free ions are left to interact throughout all reliant systems including normal bystander cells, posing detrimental effects that can lead to severe off target toxicity. − To address this issue and to further investigate the role of CsCl in metabolic therapy, a nanomedicine approach was envisioned, since nanoparticles tend to accumulate passively into tumor tissue much more than normal tissues. − This is due to the rapid and entropic metastasis of in vivo tumor growth which leads to poor formation of blood and drainage vessels in adjacent tissue; a phenomenon commonly known as the enhanced permeability and retention effect (EPR) . Nanoparticles of certain sizes tend to accumulate passively into tumor tissue much more than they do in normal tissues. − Toward this aim, we developed a nanoparticle of ionic cesium (NanoCs) for delivery to tumor cells in vitro and in vivo for the first time. The NanoCs particle was used to investigate any possible intracellular pH change from intracellular delivery of ionic cesium, mechanistic influence on glucose uptake, and ROS generation, as well as the method of cellular death.…”

Section: Introductionmentioning

confidence: 99%

Nano-Cesium for Anti-Cancer Properties: An Investigation into Cesium Induced Metabolic Interference

Daza

Misra

Schwartz-Duval

et al. 2016

ACS Appl. Mater. Interfaces

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The use of cesium chloride (CsCl) for cancer therapy ("high pH therapy") has been theorized to produce anticancer properties by raising intracellular pH to induce apoptosis. Although considered as "alternative medicine", little scientific evidence supports this theory. Alternatively, cells have no cesium ion (Cs) mediated channels for clearance. Thus, such unstable electrochemical distributions have the severe potential to disrupt electrochemical dependent cellular processes, such as glucose cotransporters. Hence, a detailed investigation of pH changing effects and glucose uptake inhibition are warranted as a possible cesium-induced anticancer therapy. We developed and characterized cesium nanoparticles (38 ± 6 nm), termed NanoCs, for nanoparticle-mediated internalization of the ion, and compared its treatment to free CsCl. Our investigations suggest that neither NanoCs nor CsCl drastically changed the intracellular pH, negating the theory. Alternatively, NanoCs lead to a significant decrease in glucose uptake when compared to free CsCl, suggesting cesium inhibited glucose uptake. An apoptosis assay of observed cell death affirms that NanoCs leads tumor cells to initiate apoptosis rather than follow necrotic behavior. Furthermore, NanoCs lead to in vivo tumor regression, where H&E analysis confirmed apoptotic cell populations. Thus, NanoCs performed pH-independent anticancer therapy by inducing metabolic stasis.

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Nano-Enabled Delivery of Intracellular Therapeutics

Cited by 3 publications

References 70 publications

Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer

Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer

Functional carbon nanodots for multiscale imaging and therapy

Nano-Cesium for Anti-Cancer Properties: An Investigation into Cesium Induced Metabolic Interference

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