Pifithrin-μ incorporated in gold nanoparticle amplifies pro-apoptotic unfolded protein response cascades to potentiate synergistic glioblastoma therapy

Zhu, Haitao; Cao, Xiongfeng; Cai, Xiaojie; Tian, Ying; Wang, Dongqing; Qi, Jianchen; Teng, Zhaogang; Lu, Guangming; Ni, Qianqian; Wang, Shouju; Zhang, Longjiang

doi:10.1016/j.biomaterials.2019.119677

Cited by 40 publications

(27 citation statements)

References 37 publications

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“…Unfortunately, the clinical application of PFTµ is hindered owing to the poor solubility, low stability and selectivity. Fortunately, it has recently been shown that nanotechnology-based delivery systems can significantly improve the pharmacokinetics and biodistribution of PFTµ [56]. Hopefully, these approaches can be developed further, allowing for more efficient and more precise targeting of the HSP70 function and better tackling of the autoimmune demyelination.…”

Section: Discussionmentioning

confidence: 99%

The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

Ćwiklińska

Cichalewska-Studzinska

Selmaj

et al. 2020

IJMS

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T helper cells type 17 (Th17) are orchestrators of autoimmune conditions, including multiple sclerosis (MS), but mechanisms of Th17 pathogenicity remain unknown. MicroRNAs (miRNA) are known to control T cells. To understand the function of miRNA in Th17, we have established a T cell line, EL4-TCR+, that resembles the expression pattern of the Th17 cells. Subsequently, we have evaluated the crosstalk between miRNA and Th17 genes’ expression using a combination of gene expression profiling, gene expression manipulation, RNA and protein immunoprecipitation, as well as confocal microscopy. We have found that Th17-related miRNA were strongly expressed in EL4-TCR+ cells following the binding of the cluster of differentiation 3 (CD3) component of the T cell receptor (TCR). Furthermore, a specific inhibition of these miRNA resulted in downregulation of the critical Th17 genes’ expression. Surprisingly, this mechanism relied on the function of the stress signal regulator heat shock protein 70 (HSP70). Upon activation, HSP70 co-localized intracellularly with miRNA processing proteins. Precipitation of HSP70 resulted in enrichment of the Th17-associated miRNA. Finally, HSP70 inhibition led to downregulation of the Th17 genes’ expression and ameliorated development of autoimmune demyelination. Our study demonstrated that HSP70 facilitates specific miRNA function leading to Th17 genes’ expression, a mechanism linking stress and autoimmunity.

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Section: Discussionmentioning

confidence: 99%

The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

Ćwiklińska

Cichalewska-Studzinska

Selmaj

et al. 2020

IJMS

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“…GNPs have been used as sensitizers for RT to increase X-ray absorption and generate local hyper heat for the thermal ablation of tumors 102 . More recently, GBNs have been used as a radiosensitizer (polydopamine-modified GNPs) and a heat shock protein A5 inhibitor, thus achieving synergistic amplification of RT, photothermal therapy, and pro-apoptotic unfolded protein reactions (Figure 5B) 103 . Excitingly, no local tumor recurrence has been observed after 14 d treatment with the multifunctional nanotheranostics in a glioma xenograft nude mouse model.…”

Section: Combination Therapymentioning

confidence: 99%

Gold-based nanomaterials for the treatment of brain cancer

Luo

et al. 2021

Cancer Biol. Med.

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Brain cancer, also known as intracranial cancer, is one of the most invasive and fatal cancers affecting people of all ages. Despite the great advances in medical technology, improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier (BBB). Fortunately, recent endeavors using gold-based nanomaterials (GBNs) have indicated the potential of these materials to cross the BBB. Therefore, GBNs might be an attractive therapeutic strategy against brain cancer. Herein, we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer treatment. Furthermore, the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized, with an emphasis on the mechanism of their effective BBB penetration. Finally, the challenges and future outlook in using GBNs for brain cancer treatment are discussed. We hope that this review will spark researchers' interest in constructing more powerful nanoplatforms for brain disease treatment.

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“…The Au nanoparticles at the core of the nanoplatforms can be used for CT imaging, and the polydopamine layer on the surface can be used for MR T1-weighted imaging. The results of the study show that after the tail vein injection of the nanomaterial, CT/MRI dual-modality imaging of brain GBM can be carried out, thereby guiding radiotherapy and photothermal therapy and realizing the integration of diagnosis and treatment [ 135 ].…”

Section: The Imaging Applications Of Inorganic Nanomaterials In Different Brain Disease Modelsmentioning

confidence: 99%

Inorganic Nanomaterial for Biomedical Imaging of Brain Diseases

Zhou

Zhang

et al. 2021

Molecules

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In the past few decades, brain diseases have taken a heavy toll on human health and social systems. Magnetic resonance imaging (MRI), photoacoustic imaging (PA), computed tomography (CT), and other imaging modes play important roles in disease prevention and treatment. However, the disadvantages of traditional imaging mode, such as long imaging time and large noise, limit the effective diagnosis of diseases, and reduce the precision treatment of diseases. The ever-growing applications of inorganic nanomaterials in biomedicine provide an exciting way to develop novel imaging systems. Moreover, these nanomaterials with special physicochemical characteristics can be modified by surface modification or combined with functional materials to improve targeting in different diseases of the brain to achieve accurate imaging of disease regions. This article reviews the potential applications of different types of inorganic nanomaterials in vivo imaging and in vitro detection of different brain disease models in recent years. In addition, the future trends, opportunities, and disadvantages of inorganic nanomaterials in the application of brain diseases are also discussed. Additionally, recommendations for improving the sensitivity and accuracy of inorganic nanomaterials in screening/diagnosis of brain diseases.

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Pifithrin-μ incorporated in gold nanoparticle amplifies pro-apoptotic unfolded protein response cascades to potentiate synergistic glioblastoma therapy

Cited by 40 publications

References 37 publications

The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

Gold-based nanomaterials for the treatment of brain cancer

Inorganic Nanomaterial for Biomedical Imaging of Brain Diseases

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