RNA m6A Alterations Induced by Biomineralization Nanoparticles: A Proof-of-Concept Study of Epitranscriptomics for Nanotoxicity Evaluation

Pan, Jinbin; Wang, Jiaojiao; Fang, Kun; Hou, Wenjing; Li, Bing; Zhao, Jie; Ma, Xiaofang

doi:10.1186/s11671-022-03663-x

Cited by 3 publications

(3 citation statements)

References 73 publications

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“…In this work, we performed a comprehensively preclinical evaluation of Gd@BSA NPs by using the medium-sized animal models of rabbits, and thus provided further evidence for their clinical translation potential. Because of the protein-based biomineralization synthesis method as previously reported, [34][35][36] ultra-small Gd@BSA NPs with a hydrodynamic diameter of <6 nm were successfully prepared by adjusting the feeding molar ratio of Gd/BSA as well as the pH environment in the reaction. The as-prepared Gd@BSA NPs exhibited excellent stability and T1 relaxivity, which were beneficial to their further biomedical applications.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of a Protein-Based Nanoscale Contrast Agent for MR Angiography at an Ultralow Dose

Li¹,

Zhang²,

Liu³

et al. 2023

IJN

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Purpose BSA-biomineralized Gd nanoparticles (Gd@BSA NPs) have been recognized as promising nanoscale MR contrast agents. The aim of this study was to carry out a preclinical evaluation of these NPs in a middle-sized animal model (rabbits). Methods New Zealand white rabbits were treated intravenously with Gd@BSA NPs (0.02 mmol Gd/kg) via a clinically-used high-pressure injector, with commercial Gd-diethylene triamine pentaacetate (Gd-DTPA)-injected group as control. Then MR angiography was performed according to the standard clinical protocol with a 3.0-T MR scanner. The SNR and CNR of the main arteries and branches were monitored. Pharmacokinetics and bioclearance were continuously evaluated in blood, urine, and feces. Gd deposition in vital organs was measured by ICP‒MS. Weight monitoring, HE staining, and blood biochemical analysis were also performed to comprehensively estimate systemic toxicity. Results The ultrasmall Gd@BSA NPs (<6 nm) exhibited high stability and T1 relaxivity. Compared to Gd-DTPA, Gd@BSA NPs demonstrated superior vascular system imaging performance at ultralow doses, especially of the cardiac artery and other main branches, and exhibited a significantly higher SNR and CNR. Notably, the Gd@BSA NPs showed a shorter half-life in blood, less retention in organs, and improved biocompatibility. Conclusion The preclinical evaluations here demonstrated that Gd@BSA NPs are promising and advantageous MR CA candidates that can be used at a low dose with excellent MR imaging performance, thus suggesting its further clinical trials and applications.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of a Protein-Based Nanoscale Contrast Agent for MR Angiography at an Ultralow Dose

Li¹,

Zhang²,

Liu³

et al. 2023

IJN

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“…Notably, the combined treatment with AuNRs and tyrosine kinases inhibitors (TKIs) eliminated the m6A-mediated TKIs cancer resistance in vivo, providing the proof-of-concept for the use of nanoparticles as an epigenetic drug for cancer therapy by targeting the epitranscriptome [ 131 ]. Recently, Pan et al reported changes in the m6A pattern (hypomethylation) evaluated by m6A-sequencing (m6A-seq) in HEK293T cells mRNAs after exposure to bovine serum albumin (BSA)-templated nanoparticles, including small AuNPs (3 nm diameter), and these results can be partially explained by the abnormal aggregation of m6A-related enzymes induced by the exposure to the nanoparticles [ 132 ]. Interestingly, the genes presenting reduced m6A were mostly involved in TGF-beta signaling, critical for cell proliferation, differentiation, and apoptosis.…”

Section: Insights Into the Molecular Effects Of Aunps In Biological S...mentioning

confidence: 99%

Mechanistic Insights into the Biological Effects of Engineered Nanomaterials: A Focus on Gold Nanoparticles

Nguyen

Falagan-Lotsch

2023

IJMS

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Nanotechnology has great potential to significantly advance the biomedical field for the benefit of human health. However, the limited understanding of nano–bio interactions leading to unknowns about the potential adverse health effects of engineered nanomaterials and to the poor efficacy of nanomedicines has hindered their use and commercialization. This is well evidenced considering gold nanoparticles, one of the most promising nanomaterials for biomedical applications. Thus, a fundamental understanding of nano–bio interactions is of interest to nanotoxicology and nanomedicine, enabling the development of safe-by-design nanomaterials and improving the efficacy of nanomedicines. In this review, we introduce the advanced approaches currently applied in nano–bio interaction studies—omics and systems toxicology—to provide insights into the biological effects of nanomaterials at the molecular level. We highlight the use of omics and systems toxicology studies focusing on the assessment of the mechanisms underlying the in vitro biological responses to gold nanoparticles. First, the great potential of gold-based nanoplatforms to improve healthcare along with the main challenges for their clinical translation are presented. We then discuss the current limitations in the translation of omics data to support risk assessment of engineered nanomaterials.

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“…Mechanistically, by retaining METTL3 expression and attenuating ALKBH5 expression, OsSx-PEG NPs increase the m 6 A-dependent mRNA degradation of hypoxia-related genes, which in turn relieves the hypoxia in the TME to enhance drug efficacy and overcome resistance [ 125 ]. Another study illustrated that newly developed bovine serum albumin (BSA)-templated Au, CuS and Gd2O3 NPs alter the global m 6 A expression level, thus impairing cell proliferation, differentiation and apoptosis [ 126 ]. NPs, such as lipid-based NPs, polymer-based NPs, and inorganic NPs, can be endocytosed by tumor-associated macrophages (TAMs) and then deliver drugs or RNAs into TAMs of the TME [ 127 – 130 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy

Zhou

Chen

et al. 2023

Mol Cancer

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Cancer immunotherapy, especially immune checkpoint therapy, has revolutionized therapeutic options by reactivating the host immune system. However, the efficacy varies, and only a small portion of patients develop sustained antitumor responses. Hence, illustrating novel strategies that improve the clinical outcome of immune checkpoint therapy is urgently needed. N6-methyladenosine (m6A) has been proved to be an efficient and dynamic posttranscriptional modification process. It is involved in numerous RNA processing, such as splicing, trafficking, translation and degradation. Compelling evidence emphasizes the paramount role of m6A modification in the regulation of immune response. These findings may provide a foundation for the rational combination of targeting m6A modification and immune checkpoints in cancer treatment. In the present review, we summarize the current landscape of m6A modification in RNA biology, and highlight the latest findings on the complex mechanisms by which m6A modification governs immune checkpoint molecules. Furthermore, given the critical role of m6A modification in antitumor immunity, we discuss the clinical significance of targeting m6A modification to improve the efficacy of immune checkpoint therapy for cancer control.

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RNA m6A Alterations Induced by Biomineralization Nanoparticles: A Proof-of-Concept Study of Epitranscriptomics for Nanotoxicity Evaluation

Cited by 3 publications

References 73 publications

Preclinical Evaluation of a Protein-Based Nanoscale Contrast Agent for MR Angiography at an Ultralow Dose

Preclinical Evaluation of a Protein-Based Nanoscale Contrast Agent for MR Angiography at an Ultralow Dose

Mechanistic Insights into the Biological Effects of Engineered Nanomaterials: A Focus on Gold Nanoparticles

Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy

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