EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

Pang, Lizhi; Shah, Harshit; Wang, Hongzhi; Shu, Dan; Qian, Steven Y.; Sathish, Venkatachalem

doi:10.1016/j.omtn.2020.08.024

Cited by 22 publications

(26 citation statements)

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“…All the animal experiments in this study were approved by the Institutional Animal Care and Use Committees at North Dakota State University. About 2 × 10 6 A549 or H1299 cells were injected into the hind flank of the nude mouse to induce tumors as we previously described [26]. The mice were randomly assigned to the following treatments: Control (treated with the same volume of the vehicle), DGLA (5 mg/mouse, oral gavage, every day), iminodibenzyl (15 mg/kg, intraperitoneal injection, daily), and DGLA+ iminodibenzyl.…”

Section: Xenografted Lung Tumor Model On Nude Micementioning

confidence: 99%

“…To seek a safer and more efficient method to treat cancers, a new anti-cancer strategy [24], as shown in Figure 1, has been recently developed. This is a very different approach than the classic COX-2 inhibitors [24][25][26]. In detail, this is a strategy that adopts more abundant ω-6s such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high level of COX expressed in most cancers to promote the formation of 8-hydroxyoctanoic acid (8-HOA) using a newly developed inhibitor, delta-5-desaturase inhibitor (D5Di).…”

Section: Introductionmentioning

confidence: 99%

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2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

et al. 2021

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Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related deaths among both men and women around the world. A lot of research attention has been directed toward diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (cyclooxygenase-2) inhibitors. This is because COX-2 is commonly overexpressed in lung cancer and also the abundance of its enzymatic product prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we introduce a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6) fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX-2 expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di does not only limit the metabolic product, PGE2, but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. In this paper, we mainly report on a novel sensor, which is based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, or Ti3C2 MXene. The preliminary results have proven to sensitively, selectively, precisely, and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. The capability of the sensor to detect trace level 8-HOA in A549 has been verified in comparison with the traditional gas chromatography–mass spectrometry (GC–MS) method. The sensing principle could be due to the unique structure and material property of Ti3C2 MXene: a multilayered structure and extremely large surface area, metallic conductivity, and ease and versatility in surface modification. All these make the Ti3C2 MXene-based sensor selectively adsorb 8-HOA molecules through effective charge transfer and lead to a measurable change in the conductivity of the material with a high signal-to-noise ratio and excellent sensitivity.

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Section: Xenografted Lung Tumor Model On Nude Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

et al. 2021

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“…All the animal experiments in this study were approved by the Institutional Animal Care and Use Committees at North Dakota State University. About 2 × 10 6 A549 cells were injected into the hind flank of the nude mouse to induce tumors as we previously described [26]. The mice were randomly assigned to the following treatments: Control (treated with the same volume of the vehicle), DGLA (5 mg/mouse, oral gavage, every day), iminodibenzyl (15 mg/kg, intraperitoneal injection, every day) and DGLA+ iminodibenzyl.…”

Section: Xenografted Lung Tumor Model On Nude Micementioning

confidence: 99%

“…So, it can be taken as an indicator of local COX activity to regulate or control lung cancer. Many efforts on treating lung cancer have been focused on the development of COX-2 inhibitors because they can be used to suppress prostaglandin E2 (PGE2) formation from COX-2-catalyzed ω-6 arachidonic acid peroxidation [23].However, most COX-2 inhibitors can severely injure the gastrointestinal tract, increase the risk of cardiovascular disease, and provide limited clinical responses [22,23].To seek a safer and more efficient method to treat cancers, a new anti-cancer strategy [24], as shown in Figure 1, has been recently developed which is a very different approach than the classic COX-2 inhibitors [24][25][26]. In detail, this is a strategy which adopts more abundant ω-6s such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high level of COX expressed in most cancers to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through using a newly developed inhibitor, delta-5-desaturase (D5Di) inhibitor.…”

Section: Introductionmentioning

confidence: 99%

2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

Wang

Sadiq

Pang

et al. 2020

The 1st International Electronic Conference on Biosensors

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Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related death among both men and women around the world. A lot of research attention has been attracted to diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (Cyclooxygenase-2) inhibitors. This is because COX-2 is commonly over expressed in lung cancer and also the abundance of its enzymatic product Prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we report a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6)fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di will not only limit the metabolic product, PGE2 but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. A novel sensor based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, Ti3C2 MXene, has proved to sensitively, selectively, precisely and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. Due to the multilayered structure and extremely large surface area, metallic conductivity and easy and versatile in surface modification, Ti3C2 MXene-based sensor will be able to selectively adsorb different molecules through physical adsorption or electrostatic attraction, and lead to a measurable change in the conductivity of the material with high signal-to-noise ratio and excellent sensitivity.

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“…Instead of direct COX-2 inhibition, knockdown of delta-5-desaturase (D5D) offers a unique approach that limits the formation of arachidonic acid (a substrate for COX-2) and promotes the peroxidation of dihomo-γ-linolenic acid leading the production of 8-hydroxyoctanoic acid (8-HOA) [ 235 ]. Pang et al incorporated the siRNA of D5D with epithelial cell adhesion molecule (EpCAM) aptamers into three-way junction RNA nanoparticles that exhibited target specific accumulation, D5D knockdown, and formation of 8-HOA in lung cancer cell lines and mouse models [ 236 ]. These D5D siRNA-loaded nanoparticles inhibited the proliferation of lung cancer cells and induce apoptosis by suppressing YAP1/TAZ axis.…”

Section: Introductionmentioning

confidence: 99%

RNA-based therapies: A cog in the wheel of lung cancer defense

et al. 2021

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Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory role of different RNAs in multiple cancer pathways makes them a rich source of targets and innovative tools for developing anticancer therapies. The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies.

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EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

Cited by 22 publications

References 50 publications

2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

RNA-based therapies: A cog in the wheel of lung cancer defense

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