Endoplasmic Reticulum Stress Provocation by Different Nanoparticles: An Innovative Approach to Manage the Cancer and Other Common Diseases

Khan, Amjad Ali; Allemailem, Khaled S.; Almatroudi, Ahmad; Almatroodi, Saleh A.; Mahzari, Ali; Alsahli, Mohammed A; Rahmani, Arshad Husain

doi:10.3390/molecules25225336

Cited by 31 publications

(27 citation statements)

References 273 publications

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“…This might have significant implications on the entry of SARS-Cov2 inside host cells. SARS-CoV-2 preferentially infects and propagates alveolar type II cells that are the precursor of gas exchanging [ 112 ], and curcumin has reportedly protected alveolar type II cells of the inflammatory lung [ 113 ]. It could be assumed that curcumin has the potential to be effective against SARS Cov-2 but, its limited oral bioavailability is a snag in its handiness.…”

Section: Polyphenolsmentioning

confidence: 99%

Role of ACE2-Ang (1–7)-Mas axis in post-COVID-19 complications and its dietary modulation

et al. 2021

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Severe acute respiratory syndrome-coronavirus-2 (COVID-19) virus uses Angiotensin-Converting Enzyme 2 (ACE2) as a gateway for their entry into the human body. The ACE2 with cleaved products have emerged as major contributing factors to multiple physiological functions and pathogenic complications leading to the clinical consequences of the COVID-19 infection Decreased ACE2 expression restricts the viral entry into the human cells and reduces the viral load. COVID-19 infection reduces the ACE2 expression and induces post-COVID-19 complications like pneumonia and lung injury. The modulation of the ACE2-Ang (1–7)-Mas (AAM) axis is also being explored as a modality to treat post-COVID-19 complications. Evidence indicates that specific food components may modulate the AAM axis. The variations in the susceptibility to COVID-19 infection and the post-COVID its complications are being correlated with varied dietary habits. Some of the food substances have emerged to have supportive roles in treating post-COVID-19 complications and are being considered as adjuvants to the COVID-19 therapy. It is possible that some of their active ingredients may emerge as the direct treatment for the COVID-19.

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Section: Polyphenolsmentioning

confidence: 99%

Role of ACE2-Ang (1–7)-Mas axis in post-COVID-19 complications and its dietary modulation

et al. 2021

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“…S7). Previous studies showed that ER stress can be induced by ATP deprivation and gold-based nanoparticles [21,56,57]. In ER-stressed cells, Ca 2 + released from the ER is taken up by mitochondria and subsequently induces mitochondrial Ca 2+ overload, eventually leading to mitochondrial oxidative stress and dysfunction [15,20].…”

Section: Ampli Cation Of Oxidative Stress By Inducing Mitochondrial Dysfunction and Potent Er Stressmentioning

confidence: 99%

“…As a player in the redox balance, endoplasmic reticulum (ER), exerts an essential role in protein synthesis/folding [20], which is prone to be in uenced by extracellular stimuli and changes in intracellular homeostasis [21]. Studies indicated that any alteration of redox homeostasis in the ER would induce ER stress, which could, in turn, promote the generation of ROS [15,20].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, promoting ER stress may lead to increased ROS production and GSH depletion. Recent ndings showed that metal-based nanoparticles (NPs), such as silver NPs [23], gold NPs [24], iron oxide NPs [25], et al, could cause cell death through the induction of ER stress [21]. Gold nanoparticles (GNPs) are emerging as novel agents for cancer treatment due to their excellent biocompatibility and molecular-recognition properties [24,26].…”

Section: Introductionmentioning

confidence: 99%

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Amplification of Oxidative Stress With Lycorine and Gold-Based Nanocomposites for Synergistic Cascade Cancer Therapy

Yang

Liang

et al. 2021

Preprint

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BackgroundDespite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy.Methods and resultsA novel nanocomposite, composed of folic acid (FA) modified mesoporous silica–coated gold nanostars (GNS@MSNs-FA) and traditional Chinese medicine Lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice.ConclusionAll these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation dramatically was able to amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without no obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.

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“…Owing to their intrinsic ER stress-inducing capacity, several nanoparticles, including silver, zinc oxide, and iron oxide nanoparticles (Fe 3 O 4 NPs), may be promising alternatives for promoting ER stress at the tumor site. 7 In addition to acting as targeted nanocarriers, these nanoparticles tend to disrupt the balance of the redox state inside the ER lumen, thereby disturbing protein folding and elevating ER stress. 8 Among these nanoparticles, the widely used dual enzyme-mimic nanocatalyst Fe 3 O 4 NPs are able to conduct tumor-specific redox targeting by utilizing the different metabolic environments between the tumor and normal tissues.…”

Section: Introductionmentioning

confidence: 99%

Dual Targeting of Endoplasmic Reticulum by Redox-Deubiquitination Regulation for Cancer Therapy

Cai¹,

Hou²,

Zhang³

et al. 2021

IJN

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Background Recently, nanocatalyst-induced endoplasmic reticulum (ER) stress for cancer therapy has been attracting considerable attention. However, cancer cells are often able to overcome ER stress-induced death by activating the unfolded protein response (UPR), making nanocatalytic monotherapy a poor defense against cancer progression. Purpose In this study, to improve the nanocatalytic treatment efficacy, a phase change material (PCM) was used to encapsulate the upstream ER stress initiator, iron oxide nanoparticles (Fe 3 O 4 NPs), and the downstream UPR modulator, PR-619. Subsequently, the tumor-homing peptide tLyP-1 was coupled to it to form tLyP-1/PR-619/Fe 3 O 4 @PCM (tPF@PCM) theranostic platform. Materials and Methods tPF@PCM was synthesized using nanoprecipitation and resolidification methods followed by the EDC/NHS cross-linking method. The targeting capacity of tPF@PCM was evaluated in vitro and in vivo using flow cytometry and magnetic resonance imaging, respectively. The therapeutic efficacy of tPF@PCM was investigated in a renal cell carcinoma mouse model. Moreover, we explored the synergistic anti-tumor mechanism by examining the intracellular reactive oxygen species (ROS), aggregated proteins, ER stress response levels, and type of cell death. Results tPF@PCM had excellent tumor-targeting properties and exhibited satisfactory photothermal-enhanced tumor inhibition efficacy both in vitro and in vivo. Specifically, the phase transition temperature (45 °C) maintained using 808 nm laser irradiation significantly increased the release and catalytic activity of the peroxidase mimic Fe 3 O 4 NPs. This strongly catalyzed the generation of hydroxyl radicals (•OH) via the Fenton reaction in the acidic tumor microenvironment. The redox imbalance subsequently resulted in an increase in the level of damaged proteins in the ER and initiated ER stress. Moreover, the pan-deubiquitinase inhibitor PR-619 blocked the “adaptive” UPR-mediated degradation of these damaged proteins, exacerbating the ER burden. Consequently, irremediable ER stress activated the “terminal” UPR, leading to apoptosis in cancer cells. Conclusion This ER stress-exacerbating strategy effectively suppresses tumorigenesis, offering novel directions for advances in the treatment of conventional therapy-resistant cancers.

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Endoplasmic Reticulum Stress Provocation by Different Nanoparticles: An Innovative Approach to Manage the Cancer and Other Common Diseases

Cited by 31 publications

References 273 publications

Role of ACE2-Ang (1–7)-Mas axis in post-COVID-19 complications and its dietary modulation

Role of ACE2-Ang (1–7)-Mas axis in post-COVID-19 complications and its dietary modulation

Amplification of Oxidative Stress With Lycorine and Gold-Based Nanocomposites for Synergistic Cascade Cancer Therapy

Dual Targeting of Endoplasmic Reticulum by Redox-Deubiquitination Regulation for Cancer Therapy

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