Engineered hypoxia-responsive albumin nanoparticles mediating mitophagy regulation for cancer therapy

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 11, 2025

Hypoxic tumors present a significant challenge in cancer therapy due to their ability adaptation low-oxygen environments, which supports tumor survival and resistance treatment. Enhanced mitophagy, the selective degradation of mitochondria by autophagy, is crucial mechanism that helps sustain cellular homeostasis hypoxic tumors. In this study, we develop an azocalix[4]arene-modified supramolecular albumin nanoparticle, co-delivers hydroxychloroquine mitochondria-targeting photosensitizer, designed induce cascaded oxidative stress regulating mitophagy for treatment These nanoparticles are hypoxia-responsive release loaded guest molecules cells. The released disrupts process, thereby increasing further weakening Additionally, upon laser irradiation, photosensitizer generates reactive oxygen species independent oxygen, inducing damage activation. dual action simultaneous spatiotemporal activation flux blockade results enhanced autophagic stress, ultimately driving cell death. Our work highlights effectiveness hydroxychloroquine-mediated combined with mitochondria-targeted cascade-amplified against has been recognized as Here, group fabricates nanoparticle codelivering (HCQ) sulfur-substituted methylated nile blue analog, capable via

Language: Английский

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Parkin modulates the hepatocellular carcinoma microenvironment by regulating PD-1/PD-L1 signalling

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Parkin-mediated mitophagy is essential for the clearance of damaged mitochondria, and it inhibits tumour development. The role in modulating immunity becoming clearer, but underlying mechanism still poorly understood.

Language: Английский

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Mitochondrial Signaling Pathways Associated with DNA Damage Responses

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6128 - 6128

Published: March 24, 2023

Under physiological and stress conditions, mitochondria act as a signaling platform to initiate biological events, establishing communication from the rest of cell. Mitochondrial adenosine triphosphate (ATP), reactive oxygen species, cytochrome C, damage-associated molecular patterns messengers in metabolism, oxidative response, bystander apoptosis, cellular senescence, inflammation response. In this review paper, mitochondrial response DNA damage was summarized. clearance via fusion, fission, mitophagy regulates quality control under conditions. On other hand, damaged release their contents into cytoplasm then mediate various pathways. The role dysfunction radiation carcinogenesis discussed, recent findings on radiation-induced radioprotective agents that targeted were presented. analysis effect, hypothesized, is critical assessing risks human health.

Language: Английский

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Mitophagy at the crossroads of cancer development: Exploring the role of mitophagy in tumor progression and therapy resistance

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(6), P. 119752 - 119752

Published: May 20, 2024

Language: Английский

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miR-218-5p and doxorubicin combination enhances anticancer activity in breast cancer cells through Parkin-dependent mitophagy inhibition

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 21, 2024

Abstract Breast Cancer (BC) is one of the most common tumours, and known for its ability to develop resistance chemotherapeutic treatments. Autophagy has been linked response in several types cancer, highlighting contribution this process. However, role mitophagy, a selective form autophagy responsible damaged mitochondria degradation, therapies BC still unclear. In order address point, we analysed mitophagy treatment anticancer drug, doxorubicin (DXR), different models BC, such as luminal A subtype-BC cell line MCF7 cells, cultured 2-Dimension (2D) or 3-Dimension (3D), triple negative (TNBC) MDA-MB-231. Through microarray analysis, identified relationship between gene expressions related canonical PINK1/Parkin-mediated pathway DXR cells. Afterwards, demonstrated that PINK1/Parkin-dependent indeed induced following exogenous expression small non-coding RNA, miRNA-218-5p, target mRNA Parkin, was sufficient inhibit DXR-mediated MDA-MB-231 thereby increasing their sensitivity DXR. Considering current challenges involved refractory treatment, our work could provide promising approach prevent tumour recurrence, potentially leading development an innovative combine inhibition chemotherapy.

Language: Английский

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Targeting cellular mitophagy as a strategy for human cancers

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 5, 2024

Mitophagy is the cellular process to selectively eliminate dysfunctional mitochondria, governing number and quality of mitochondria. Dysregulation mitophagy may lead accumulation damaged which plays an important role in initiation development tumors. includes ubiquitin-dependent pathways mediated by PINK1/Parkin non-ubiquitin dependent mitochondrial autophagic receptors including NIX, BNIP3, FUNDC1. Cellular widely participates multiple metabolic reprogramming, anti-tumor immunity, ferroptosis, as well interaction between tumor cells tumor-microenvironment. And also regulates proliferation metastasis, stemness, chemoresistance, resistance targeted therapy radiotherapy. In this review, we summarized underlying molecular mechanisms discussed complex diverse contexts tumors, indicating it a promising target mitophagy-related therapy.

Language: Английский

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Mitochondrial nucleic acids in innate immunity and beyond

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(12), P. 2508 - 2518

Published: Dec. 1, 2023

Abstract Mitochondria participate in a wide range of cellular processes. One essential function mitochondria is to be platform for antiviral signaling proteins during the innate immune response viral infection. Recently, studies have revealed that mitochondrion-derived DNAs and RNAs are recognized as non-self molecules act immunogenic ligands. More importantly, cytosolic release these mitochondrial nucleic acids (mt-NAs) closely associated with pathogenesis human diseases accompanying aberrant activation. The (mtDNAs) via BAX/BAK activation and/or VDAC1 oligomerization activates inflammasome assembly. In addition, double-stranded (mt-dsRNAs) sensed by pattern recognition receptors cytosol induce type I interferon expression initiate apoptotic programs. Notably, mt-NAs also mediate adipocyte differentiation contribute mitogenesis thermogenesis. this review, we summarize recent pathways regulated mt-NAs, emerging physiological roles mt-NAs.

Language: Английский

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Interventing mitochondrial PD-L1 suppressed IFN-γ-induced cancer stemness in hepatocellular carcinoma by sensitizing sorafenib-induced ferroptosis

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 212, P. 360 - 374

Published: Jan. 1, 2024

Language: Английский

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Mitophagy: insights into its signaling molecules, biological functions, and therapeutic potential in breast cancer

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 29, 2024

Abstract Mitophagy, a form of selective autophagy that removes damaged or dysfunctional mitochondria, plays crucial role in maintaining mitochondrial and cellular homeostasis. Recent findings suggest defective mitophagy is closely associated with various diseases, including breast cancer. Moreover, better understanding the multifaceted roles cancer progression for treatment this disease. Here, we will summarize molecular mechanisms process. In addition, highlight expression patterns mitophagy-related signaling molecules potential implications development cancer, aiming to provide therapeutic strategies treatment.

Language: Английский

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Mitophagy in hypertension-mediated organ damage

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 10

Published: Jan. 4, 2024

Hypertension constitutes a pervasive chronic ailment on global scale, frequently inflicting damage upon vital organs, such as the heart, blood vessels, kidneys, brain, and others. And this is complex clinical dilemma that requires immediate attention. The mitochondria assume crucial function in generation of energy, it utmost importance to eliminate any malfunctioning or surplus uphold intracellular homeostasis. Mitophagy considered classic example selective autophagy, an important component mitochondrial quality control, closely associated with many physiological pathological processes. ubiquitin-dependent pathway, facilitated by PINK1/Parkin, along ubiquitin-independent orchestrated receptor proteins BNIP3, NIX, FUNDC1, represent extensively investigated mechanisms underlying mitophagy. In recent years, research has increasingly shown mitophagy plays role organ hypertension. Exploring molecular hypertension-mediated could critical avenue for future development innovative therapeutic modalities. Therefore, article provides comprehensive review impact due

Language: Английский

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