Impairment of mitochondrial dynamics involved in iron oxide nanoparticle‐induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3‐methyladenine

Zhang, Tian‐guang; Zhou, Qianqian; Wang, Xiaohui; Zhan, Lin‐sheng

doi:10.1002/jat.3933

Cited by 14 publications

(9 citation statements)

References 43 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This adjuvant effect of IONPs was also demonstrated by Zhao et al in an OVA-based vaccine model by administering OVA@IONPs to OVA-expressing CT26 tumor-bearing mice, which produced a significant delay in tumor growth [ 184 ]. Zhang et al, however, revealed that PEG-coated IONPs disturbed mitochondrial dynamics through an increase in autophagy, and as a consequence, treated immature DCs exhibited downregulation of co-stimulatory molecules such as CD86, CD80, and CCR7, as well as reduced phagocytic capacity [ 185 ]. Therefore, as seen in macrophages, the effects of IONPs on DCs is variable and depends on a plethora of factors such as IONP size, shape, and coating, as well as DC maturation status, among others.…”

Section: Ionp Effects Is Dependent On Cell Type and Statusmentioning

confidence: 99%

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

2020

View full text Add to dashboard Cite

Over the last 20 years, iron oxide nanoparticles (IONPs) have been the subject of increasing investigation due to their potential use as theranostic agents. Their unique physical properties (physical identity), ample possibilities for surface modifications (synthetic identity), and the complex dynamics of their interaction with biological systems (biological identity) make IONPs a unique and fruitful resource for developing magnetic field-based therapeutic and diagnostic approaches to the treatment of diseases such as cancer. Like all nanomaterials, IONPs also interact with different cell types in vivo, a characteristic that ultimately determines their activity over the short and long term. Cells of the mononuclear phagocytic system (macrophages), dendritic cells (DCs), and endothelial cells (ECs) are engaged in the bulk of IONP encounters in the organism, and also determine IONP biodistribution. Therefore, the biological effects that IONPs trigger in these cells (biological identity) are of utmost importance to better understand and refine the efficacy of IONP-based theranostics. In the present review, which is focused on anti-cancer therapy, we discuss recent findings on the biological identities of IONPs, particularly as concerns their interactions with myeloid, endothelial, and tumor cells. Furthermore, we thoroughly discuss current understandings of the basic molecular mechanisms and complex interactions that govern IONP biological identity, and how these traits could be used as a stepping stone for future research.

show abstract

Section: Ionp Effects Is Dependent On Cell Type and Statusmentioning

confidence: 99%

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

2020

View full text Add to dashboard Cite

show abstract

“…Our previous study has indicated that mitochondrial dynamics shifts toward Drp1-dependent mitochondrial fission in immune cells during sepsis and Mdivi-1, as a selective inhibitor of Drp1, reduced the apoptosis of immune cells through inhibiting mitochondrial fission (Wu et al 2019 ). Moreover, an increase in mitochondrial fission contributes to the dysfunction of DC (Zhang et al 2020 ). To determine the role of PINK1 in LPS-induced mitochondrial quality control, we secondly evaluated the induction of mitochondrial dynamics in DCs isolated from WT and PINK1 −/− mice following LPS treatment.…”

Section: Resultsmentioning

confidence: 99%

PINK1 protects against dendritic cell dysfunction during sepsis through the regulation of mitochondrial quality control

Chen

Qiu

et al. 2023

Mol Med

View full text Add to dashboard Cite

Background Dendritic cell (DC) dysfunction plays a central role in sepsis-induced immunosuppression. Recent research has indicated that collective mitochondrial fragmentation contributes to the dysfunction of immune cells observed during sepsis. PTEN-induced putative kinase 1 (PINK1) has been characterized as a guide for impaired mitochondria that can keep mitochondrial homeostasis. However, its role in the function of DCs during sepsis and the related mechanisms remain obscure. In our study, we elucidated the effect of PINK1 on DC function during sepsis and its underlying mechanism of action. Methods Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) treatment were used as in vivo and in vitro sepsis models, respectively. Results We found that changes in mitochondrial PINK1 expression of DCs paralleled changes in DC function during sepsis. The ratio of DCs expressing MHC-II, CD86, and CD80, the mRNAs level of dendritic cells expressing TNF-α and IL-12, and the level of DC-mediated T-cell proliferation were all decreased, both in vivo and in vitro during sepsis, when PINK1 was knocked out. This suggested that PINK1 knockout prevented the function of DCs during sepsis. Furthermore, PINK1 knockout inhibited Parkin RBR E3 ubiquitin protein (Parkin)-dependent mitophagy and enhanced dynamin-related protein 1 (Drp1)-related mitochondrial fission, and the negative effects of PINK1 knockout on DC function following LPS treatment were reversed by Parkin activation and Drp1 inhibitor. Knockout of PINK1 also increased apoptosis of DCs and the mortality of CLP mice. Conclusion Our results indicated that PINK1 protected against DC dysfunction during sepsis through the regulation of mitochondrial quality control.

show abstract

“…Not surprisingly, rats treated with IONPs for 14 days did not exhibit severe inflammatory or toxic reactions based on the roles of autophagy in stress adaptation, immune, and inflammatory response ( Cadwell, 2016 ). However, some studies showed that IONPs caused cell damage by inducing autophagy ( Du et al, 2016 ; Zhang et al, 2020 ). Therefore, the role of autophagy in IONPs toxicity remains to be further elucidated.…”

Section: Discussionmentioning

confidence: 99%

Proteomics unite traditional toxicological assessment methods to evaluate the toxicity of iron oxide nanoparticles

Han¹,

Tian²,

Wang³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Iron oxide nanoparticles (IONPs) are the first generation of nanomaterials approved by the Food and Drug Administration for use as imaging agents and for the treatment of iron deficiency in chronic kidney disease. However, several IONPs-based imaging agents have been withdrawn because of toxic effects and the poor understanding of the underlying mechanisms. This study aimed to evaluate IONPs toxicity and to elucidate the underlying mechanism after intravenous administration in rats. Seven-week-old rats were intravenously administered IONPs at doses of 0, 10, 30, and 90 mg/kg body weight for 14 consecutive days. Toxicity and molecular perturbations were evaluated using traditional toxicological assessment methods and proteomics approaches, respectively. The administration of 90 mg/kg IONPs induced mild toxic effects, including abnormal clinical signs, lower body weight gain, changes in serum biochemical and hematological parameters, and increased organ coefficients in the spleen, liver, heart, and kidneys. Toxicokinetics, tissue distribution, histopathological, and transmission electron microscopy analyses revealed that the spleen was the primary organ for IONPs elimination from the systemic circulation and that the macrophage lysosomes were the main organelles of IONPs accumulation after intravenous administration. We identified 197 upregulated and 75 downregulated proteins in the spleen following IONPs administration by proteomics. Mechanically, the AKT/mTOR/TFEB signaling pathway facilitated autophagy and lysosomal activation in splenic macrophages. This is the first study to elucidate the mechanism of IONPs toxicity by combining proteomics with traditional methods for toxicity assessment.

show abstract

Impairment of mitochondrial dynamics involved in iron oxide nanoparticle‐induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3‐methyladenine

Cited by 14 publications

References 43 publications

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

PINK1 protects against dendritic cell dysfunction during sepsis through the regulation of mitochondrial quality control

Proteomics unite traditional toxicological assessment methods to evaluate the toxicity of iron oxide nanoparticles

Contact Info

Product

Resources

About