CX-5461-loaded nucleolus-targeting nanoplatform for cancer therapy through induction of pro-death autophagy

Duo, Yanhong; Yang, Min; Du, Zhenya; Feng, Chu-Han; Chen, Xing; Wu, Yanping; Xie, Zhizhong; Zhang, Fang; Huang, Laiqiang; Zeng, Xiaowei; Chen, Hongbo

doi:10.1016/j.actbio.2018.08.035

Cited by 50 publications

(26 citation statements)

References 41 publications

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“…Recently, CX-5461 was loaded on a nanoplatform to enrich for nucleolar accumulation of the drug in order to enhance the anti-cancer effect, without causing significant side effects. In vivo and in vitro assays confirm induction of pro-death autophagy in HeLa cells, as well anti-proliferative and anti-tumor effects (Duo et al, 2018).…”

Section: Nucleolar Stress and Autophagy: A Tight Regulation Between Hmentioning

confidence: 89%

Emerging Role of the Nucleolar Stress Response in Autophagy

Pfister

2019

Front. Cell. Neurosci.

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Autophagy represents a conserved self-digestion program, which allows regulated degradation of cellular material. Autophagy is activated by cellular stress, serum starvation and nutrient deprivation. Several autophagic pathways have been uncovered, which either non-selectively or selectively target the cellular cargo for lysosomal degradation. Autophagy engages the coordinated action of various key regulators involved in the steps of autophagosome formation, cargo targeting and lysosomal fusion. While non-selective (macro)autophagy is required for removal of bulk material or recycling of nutrients, selective autophagy mediates specific targeting of damaged organelles or protein aggregates. By proper action of the autophagic machinery, cellular homeostasis is maintained. In contrast, failure of this fundamental process is accompanied by severe pathophysiological conditions. Hallmarks of neuropathological disorders are for instance accumulated, mis-folded protein aggregates and damaged mitochondria. The nucleolus has been recognized as central hub in the cellular stress response. It represents a sub-nuclear organelle essential for ribosome biogenesis and also functions as stress sensor by mediating cell cycle arrest or apoptosis. Thus, proper nucleolar function is mandatory for cell growth and survival. Here, I highlight the emerging role of nucleolar factors in the regulation of autophagy. Moreover, I discuss the nucleolar stress response as a novel signaling pathway in the context of autophagy, health and disease.

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Section: Nucleolar Stress and Autophagy: A Tight Regulation Between Hmentioning

confidence: 89%

Emerging Role of the Nucleolar Stress Response in Autophagy

Pfister

2019

Front. Cell. Neurosci.

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“…Aptamers are small, highly sensitive, biodegradable, and have immunogenicity, making them good candidates for active targeting ligands [33]. In 2018, Duo et al used the AS-1411 aptamer to target mesoporous silica NPs containing CX-5461 to the nucleus of tumor cells (Figure 3) [34]. The AS-1411 G-rich DNA aptamer specifically recognizes nucleolin, a protein upregulated in many cancer cell lines.…”

Section: Biological Ligands and Their Applications For Nanoparticlesmentioning

confidence: 99%

“…Scheme of CX-5461-loaded mesoporous silica NPs modified with AS-1411 aptamers to increase nucleoli targeting. Reproduced with permission from Reference [34].…”

Section: Figures Scheme and Tablementioning

confidence: 99%

Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems

Yoo

Park

et al. 2019

Cancers

520

267

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Targeting nanoparticle (NP) carriers to sites of disease is critical for their successful use as drug delivery systems. Along with optimization of physicochemical properties, researchers have focused on surface modification of NPs with biological ligands. Such ligands can bind specific receptors on the surface of target cells. Furthermore, biological ligands can facilitate uptake of modified NPs, which is referred to as ‘active targeting’ of NPs. In this review, we discuss recent applications of biological ligands including proteins, polysaccharides, aptamers, peptides, and small molecules for NP-mediated drug delivery. We prioritized studies that have demonstrated targeting in animals over in vitro studies. We expect that this review will assist biomedical researchers working with NPs for drug delivery and imaging.

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“…The anticancer properties of this nanoplatform were due to the inhibition of rRNA transcription and activation of pro-death autophagy. It is of interest that the CX-5461-loaded nanoplatform did not exhibit any relevant toxicity, identifying it as a safe and potentially nucleolus-targeting anticancer drug [ 130 ].…”

Section: Autophagy In Cell Response To Cancer Treatmentmentioning

confidence: 99%

Role of Autophagy in Cancer Cell Response to Nucleolar and Endoplasmic Reticulum Stress

Pecoraro

Pagano

Russo

et al. 2020

IJMS

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Eukaryotic cells are exposed to many internal and external stimuli that affect their fate. In particular, the exposure to some of these stimuli induces stress triggering a variety of stress responses aimed to re-establish cellular homeostasis. It is now established that the deregulation of stress response pathways plays a central role in cancer initiation and progression, allowing the adaptation of cells to an altered state in the new environment. Autophagy is a tightly regulated pathway which exerts “housekeeping” role in physiological processes. Recently, a growing amount of evidence highlighted the crucial role of autophagy in the regulation of integrated stress responses, including nucleolar and endoplasmic reticulum. In this review, we attempt to afford an overview of the complex role of nucleolar and endoplasmic reticulum stress-response mechanisms in the regulation of autophagy in cancer and cancer treatment.

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CX-5461-loaded nucleolus-targeting nanoplatform for cancer therapy through induction of pro-death autophagy

Cited by 50 publications

References 41 publications

Emerging Role of the Nucleolar Stress Response in Autophagy

Emerging Role of the Nucleolar Stress Response in Autophagy

Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems

Role of Autophagy in Cancer Cell Response to Nucleolar and Endoplasmic Reticulum Stress

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