Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation

Theranostics, Journal Year: 2023, Volume and Issue: 13(2), P. 736 - 766

Published: Jan. 1, 2023

Cellular mitophagy means that cells selectively wrap and degrade damaged mitochondria through an autophagy mechanism, thus maintaining intracellular homeostasis.In recent years, has received increasing attention as a research hotspot related to the pathogenesis of clinical diseases, such neurodegenerative cardiovascular cancer, metabolic so on.It been found regulation may become new direction for treatment some diseases.In addition, numerous small molecule modulators have also reported, which provides opportunities comprehend procedure potential therapeutic development.Taken together, in this review, we summarize current understanding mechanism mitophagy, discuss roles its relationship with introduce existing small-molecule pharmacological further highlight significance their development.

Language: Английский

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Theranostic Fluorescent Probes

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(5), P. 2699 - 2804

Published: Feb. 29, 2024

The ability to gain spatiotemporal information, and in some cases achieve control, the context of drug delivery makes theranostic fluorescent probes an attractive intensely investigated research topic. This interest is reflected steep rise publications on topic that have appeared over past decade. Theranostic probes, their various incarnations, generally comprise a fluorophore linked masked drug, which released as result certain stimuli, with both intrinsic extrinsic stimuli being reported. release then signaled by emergence signal. Importantly, use appropriate fluorophores has enabled not only this emerging fluorescence marker for but also provided modalities useful photodynamic, photothermal, sonodynamic therapeutic applications. In review we highlight recent work particular focus are activated tumor microenvironments. We summarize efforts develop other applications, such neurodegenerative diseases antibacterials. celebrates diversity designs reported date, from discrete small-molecule systems nanomaterials. Our aim provide insights into potential clinical impact still-emerging direction.

Language: Английский

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Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 18, 2022

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cells response to therapy-induced hostile environment are largely unknown. As central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes integrate signaling pathways provide bioenergetic biosynthetic flexibility cells, which contributes multiple aspects tumor characteristics, including drug resistance. Therefore, targeting therapy overcoming has attracted increasing attention various types cancer. Multiple mitochondrial processes, dynamics, metabolism, apoptotic regulatory machinery, have been demonstrated be potential targets. However, recent insights into revealed complexity structure functions, elusive functions biology, inaccessibility mitochondria, posed challenges clinical application mitochondrial-based therapeutic strategies. discovery both novel mitochondria-targeting agents innovative approaches is urgently required. Here, we review most literature summarize molecular their intricate connection with In addition, an overview emerging strategies target effectively chemoresistance highlighted, emphasis on repositioning delivery approaches, may accelerate compounds therapy.

Language: Английский

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Dynamic Assembly of DNA Nanostructures in Living Cells for Mitochondrial Interference

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(10), P. 4667 - 4677

Published: March 7, 2022

Constructing artificial dynamic architectures inside cells to rationally interfere with organelles is emerging as an efficient strategy regulate the behaviors and fate of cells, thus providing new routes for therapeutics. Herein, we develop intracellular K+-mediating assembly DNA tetrahedrons which realizes mitochondrial interference consequent regulation on energy metabolism living cells. In designer tetrahedron, one vertex was modified triphenylphosphine (TPP) targeting, other three vertexes were tethered guanine-rich sequences that could realize formation intermolecular G-quadruplexes, consequently led form aggregates in cytoplasm. The specially targeted mitochondria served a polyanionic barrier substance communication, generating significant inhibition effect aerobic respiration function associated glycolysis process, reduced production adenosine triphosphate (ATP). lack ATP impeded lamellipodium essential movement resulting inhibitory cell migration. Remarkably, migration capacity suppressed by high 50% cancer This work provides manipulation via endogenous molecule-mediating exogenous envisioned have great potential precise biomedicine.

Language: Английский

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Unraveling mitochondria‐targeting reactive oxygen species modulation and their implementations in cancer therapy by nanomaterials

Exploration, Journal Year: 2023, Volume and Issue: 3(2)

Published: April 1, 2023

Abstract Functional subcellular organelle mitochondria are emerging as a crucial player and driver of cancer. For maintaining the sites cellular respiration, experience production, accumulation reactive oxygen species (ROS) underlying oxidative damage in electron transport chain carriers. Precision medicine targeting can change nutrient availability redox homeostasis cancer cells, which might represent promising strategy for suppressing tumor growth. Herein, this review highlights how modification capable manipulating nanomaterials ROS generation strategies influence or compensate state mitochondrial homeostasis. We propose foresight to guide research innovation with an overview seminal work discuss future challenges our perspective on commercialization novel mitochondria‐targeting agents.

Language: Английский

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Organelle-targeted therapies: a comprehensive review on system design for enabling precision oncology

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 19, 2022

Abstract Cancer is a major threat to human health. Among various treatment methods, precision therapy has received significant attention since the inception, due its ability efficiently inhibit tumor growth, while curtailing common shortcomings from conventional cancer treatment, leading towards enhanced survival rates. Particularly, organelle-targeted strategies enable precise accumulation of therapeutic agents in organelles, locally triggering organelle-mediated cell death signals which can greatly reduce threshold dosage and minimize side-effects. In this review, we comprehensively discuss history recent advances targeted therapies on specifically including nucleus, mitochondria, lysosomes endoplasmic reticulum, focusing organelle structures, signal pathways, design guidelines nanomedicines based intervention mechanisms. Furthermore, perspective future research clinical opportunities potential challenges oncology presented. Through demonstrating developments therapies, believe article further stimulate broader interests multidisciplinary technology development for enabling advanced their corresponding clinic translations.

Language: Английский

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Mitochondria‐Targeting Phototheranostics by Aggregation‐Induced NIR‐II Emission Luminogens: Modulating Intramolecular Motion by Electron Acceptor Engineering for Multi‐Modal Synergistic Therapy

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(16)

Published: Jan. 10, 2022

Abstract Phototheranostic agents have thrived as promising tools for cancer theranostics because of the integration sensitive in situ fluorescence imaging and effective multi‐model synergistic therapy. However, how to manipulate intangible photon energy transfer balance competitive radiative nonradiative processes is still challenging. Although numerous phototheranostic molecules are reported, their complicated molecular design tedious synthesis often stumble further development. Herein, three simple with electron donating−accepting structures developed. The acceptor engineering on by introducing acridinium unit gives rise TPEDCAc aggregation‐induced second near‐infrared emission (AIE NIR‐II), high reactive oxygen species generation capability, excellent photothermal conversion efficiency (44.8%) due drastic intramolecular motion large rotor balanced AIE effect. Experimental analysis calculation controlled suggested that torsional angle strong electron‐withdrawing ability keys NIR‐II photodynamic/photothermal conversion. Impressively, positively charged shows mitochondria‐targeting capability performance vivo multi‐modal under NIR laser irradiation. Hence, this work not only provides a single AIE‐based theranostic system but inspires new insights into future development platforms.

Language: Английский

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Stimulus-responsive self-assembled prodrugs in cancer therapy

Chemical Science, Journal Year: 2022, Volume and Issue: 13(15), P. 4239 - 4269

Published: Jan. 1, 2022

Small-molecule prodrugs have become the main toolbox to improve unfavorable physicochemical properties of potential therapeutic compounds in contemporary anti-cancer drug development. Many approved small-molecule prodrugs, however, still face key challenges their pharmacokinetic (PK) and pharmacodynamic (PD) properties, thus severely restricting further clinical applications. Self-assembled emerged as they could take advantage benefits both prodrug design nanomedicine, so maximize loading, reduce premature leakage, PK/PD parameters targeting ability. Notably, temporally spatially controlled release drugs at cancerous sites be achieved by encoding various activable linkers that are sensitive chemical or biological stimuli tumor microenvironment (TME). In this review, we comprehensively summarized recent progress made development single/multiple-stimulus-responsive self-assembled for mono- combinatorial therapy. A special focus was placed on conjugation strategies (polymer-drug conjugates, drug-drug

Language: Английский

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Nanoparticle‐Based Photothermal Therapy for Breast Cancer Noninvasive Treatment

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 10, 2023

Rapid advancements in materials science and nanotechnology, intertwined with oncology, have positioned photothermal therapy (PTT) as a promising noninvasive treatment strategy for cancer. The breast's superficial anatomical location aesthetic significance render breast cancer particularly pertinent candidate the clinical application of PTT following melanoma. This review comprehensively explores research conducted on various types nanoparticles employed elaborates their specific roles mechanisms action. integration existing therapies is scrutinized, underscoring its potential synergistic outcomes. Additionally, underlying consequential modifications to tumor microenvironment after are elaborated from medical perspective. Future directions suggested, an emphasis development integrative platforms that combine multiple therapeutic approaches optimization nanoparticle synthesis enhanced efficacy. goal push boundaries toward comprehensive, clinically applicable

Language: Английский

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In Response to Precision Medicine: Current Subcellular Targeting Strategies for Cancer Therapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(21)

Published: Nov. 29, 2022

Abstract Emerging as a potent anticancer treatment, subcellular targeted cancer therapy has drawn increasing attention, bringing great opportunities for clinical application. Here, two targeting strategies four main organelles (mitochondria, lysosome, endoplasmic reticulum, and nucleus), including molecule‐ nanomaterial (inorganic nanoparticles, micelles, organic polymers, others)‐based delivery or therapeutic strategies, are summarized. Phototherapy, chemotherapy, radiotherapy, immunotherapy, “all‐in‐one” combination among the covered in detail. Such materials constructed based on specific properties relevant mechanisms of organelles, enabling elimination tumors by inducing dysfunction corresponding destroying structures. The challenges faced organelle‐targeting therapies also Looking forward, paradigm with enhanced efficacy compared to current approaches is envisioned.

Language: Английский

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