Rational Designs at the Forefront of Mitochondria-Targeted Gene Delivery: Recent Progress and Future Perspectives

ACS Biomaterials Science & Engineering, Год журнала: 2022, Номер 8(2), С. 348 - 359

Опубликована: Янв. 3, 2022

Mitochondria play an essential role in cellular metabolism and generate energy cells. To support these functions, several proteins are encoded the mitochondrial DNA (mtDNA). The mutation of mtDNA causes dysfunction ultimately results a variety inherited diseases. date, gene delivery systems targeting mitochondria have been developed to ameliorate mutations. However, applications strategies therapy still being explored optimized. Thus, from this perspective, we herein highlight recent mitochondria-targeting for discuss future directions effective mitochondria-targeted delivery.

Язык: Английский

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Targeting Mitochondria with ClpP Agonists as a Novel Therapeutic Opportunity in Breast Cancer

Cancers, Год журнала: 2023, Номер 15(7), С. 1936 - 1936

Опубликована: Март 23, 2023

Breast cancer is the most frequently diagnosed malignancy worldwide and leading cause of mortality in women. Despite recent development new therapeutics including targeted therapies immunotherapy, triple-negative breast remains an aggressive form cancer, thus improved treatments are needed. In decades, it has become increasingly clear that cancers harbor metabolic plasticity controlled by mitochondria. A myriad studies provide evidence mitochondria essential to progression. Mitochondria widely reprogrammed enhance energy production biosynthesis macromolecules required for tumor growth. this review, we will discuss current understanding mitochondrial roles elucidate why a rational therapeutic target. We then outline status use mitochondria-targeting drugs cancers, highlight ClpP agonists as emerging with unique mechanism action. also illustrate possible drug combination strategies challenges future clinic.

Язык: Английский

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Mitochondrial signaling pathways and their role in cancer drug resistance

Cellular Signalling, Год журнала: 2024, Номер 122, С. 111329 - 111329

Опубликована: Авг. 5, 2024

Язык: Английский

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Mitochondria-targeted nanoparticles (mitoNANO): An emerging therapeutic shortcut for cancer

Biomaterials and Biosystems, Год журнала: 2021, Номер 3, С. 100023 - 100023

Опубликована: Авг. 13, 2021

The early understanding of mitochondria posited that they were 'innocent organelles' solely devoted to energy production and utilisation. Intriguingly, recent findings have outlined in detail the 'modern-day' view are an important but underappreciated drug target. Mitochondria been implicated pathophysiology many human diseases, ranging from neurodegenerative disorders cardiovascular diseases infections cancer. It is now clear normal mitochondrial function involves building blocks a cell generate lipids, proteins nucleic acids thereby facilitating growth. On other hand, dysfunction reprograms crucial cellular functions into pathological pathways, considered as integral hallmark Therefore, strategies target can provide wealth new therapeutic approaches fight against cancer, by overcoming number problems associated with conventional pharmaceutical drugs, including low solubility, poor bioavailability non-selective biodistribution. combination nanoparticles 'classical' chemotherapeutic drugs create biocompatible, multifunctional mitochondria-targeted nanoplatforms has recently studied. This approach rapidly expanding for targeted delivery systems, hybrid nanostructures be activated light (photodynamic and/or photothermal therapy). selective elegant shortcut more selective, targeted, safer cancer treatment. We propose use termed "mitoNANO". present minireview sheds on design application mitoNANO advanced therapeutics, may overcome resistance show fewer side effects.

Язык: Английский

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Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Molecules, Год журнала: 2021, Номер 27(1), С. 148 - 148

Опубликована: Дек. 27, 2021

Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, they always play important roles various biological functions abnormal pathological processes. Evaluated ROS have frequently been observed cancers to activate multiple pro-tumorigenic signaling pathways induce the survival proliferation of cancer cells. Hydrogen peroxide (H2O2) superoxide anion (O2•−) most redox agents cells, homeostasis which is maintained by dozens growth factors, cytokines, antioxidant enzymes. Therefore, enzymes tend higher activity levels maintain Effective intervention cells chelating or metal complexes has already developed into an anti-cancer strategy. We can inhibit using chelators complexes; on other hand, we also use directly regulate level via mitochondria. In this review, with regulation capacity applications collectively comprehensively analyzed, beneficial for development next generation inorganic drugs based regulation. expect that review will provide a new perspective develop novel reagents killing and, further, as candidates clinical drugs.

Язык: Английский

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A Nanomedicine Structure–Activity Framework for Research, Development, and Regulation of Future Cancer Therapies

ACS Nano, Год журнала: 2022, Номер 16(11), С. 17497 - 17551

Опубликована: Ноя. 2, 2022

Despite their clinical success in drug delivery applications, the potential of theranostic nanomedicines is hampered by mechanistic uncertainty and a lack science-informed regulatory guidance. Both therapeutic efficacy toxicity nanoformulations are tightly controlled complex interplay nanoparticle's physicochemical properties individual patient/tumor biology; however, it can be difficult to correlate such information with observed outcomes. Additionally, as nanomedicine research attempts gradually move away from large-scale animal testing, need for computer-assisted solutions evaluation will increase. Such models depend on clear understanding structure–activity relationships. This review provides comprehensive overview field cancer knowledge framework foundational interaction maps that facilitate future research, assessments, regulation. By forming three complementary profiling nanobio interactions pathways at different levels biological complexity, picture journey through body adverse consequences each presented.

Язык: Английский

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In Vitro and In Vivo Antitumor Assay of Mitochondrially Targeted Fluorescent Half-Sandwich Iridium(III) Pyridine Complexes

Inorganic Chemistry, Год журнала: 2023, Номер 62(8), С. 3395 - 3408

Опубликована: Фев. 10, 2023

Half-sandwich iridium(III) complexes show potential value in the anticancer field. However, with favorable luminescence performance are rare, which limits further investigation of mechanism. In this paper, 10 triphenylamine-modified fluorescent half-sandwich pyridine {[(η5-Cpx)Ir(L)Cl2]} (Ir1-Ir10) were prepared and showed antiproliferative activity, effectively inhibiting migration A549 cells. Ir6, showing best activity among these complexes, exhibited excellent fluorescence (absolute quantum yield 15.17%) solution. Laser confocal detection that Ir6 followed an energy-dependent cellular uptake mechanism, specifically accumulating mitochondria (Pearson co-localization coefficient 0.95). A Western blot assay confirmed existence a mitochondrial apoptotic channel. Additionally, could arrest cell cycle at G2/M phase, catalyze NADH oxidation, reduce membrane potential, induce increase level intracellular reactive oxygen species, exhibit mechanism oxidation. An vivo antitumor can inhibit tumor growth is safer than cisplatin.

Язык: Английский

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Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis

Free Radical Biology and Medicine, Год журнала: 2024, Номер 220, С. 28 - 42

Опубликована: Апрель 27, 2024

Cancer of the head and neck encompasses a wide range cancers, including oral oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages has dismal prognosis. Piscidin-1, marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated possible anti-oral effects piscidin-1 clarified mechanisms underlying these effects. treated squamous cell carcinoma lines OC2 SCC4 with Piscidin-1. Cell viability expression different hallmark apoptotic molecules, reactive oxygen species (ROS), were tested using appropriate MTT assay, flow cytometry western blotting assays, human umbilical vein endothelial (HUVEC) wound healing, migration, tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. ROS intensifies oxidative stress in endoplasmic reticulum mitochondria, causing mitochondrial dysfunction. Additionally, it decreases consumption rates activity complexes I–V. As expected, antioxidants MitoTEMPOL N-acetylcysteine reduce Piscidin-1–induced generation intracellular calcium accumulation. inhibits matrix metalloproteinase (MMP)-2/-9 HUVECs, affecting migration angiogenesis. demonstrated that can promote apoptosis via both intrinsic extrinsic pathways findings indicate anti-proliferative anti-angiogenic properties treatment. Our study on thus provides basis for future translational drug research new theoretical approach clinical research.

Язык: Английский

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Assessing the Efficacy of Mitochondria-Accumulating Self-Assembly Peptides in Pancreatic Cancer: An Animal Study

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 784 - 784

Опубликована: Янв. 17, 2025

Although pancreatic cancer presents with one of the most unfavorable prognoses, its treatment options are very limited. Mitochondria-targeting moieties, considered a new and prominent modality, expected to demonstrate synergistic anticancer effects due their distinct mechanism compared conventional chemotherapeutic approaches. This study evaluated therapeutic potential mitochondria-accumulating self-assembly peptides, referred as Mito-FFs, utilizing both in vitro vivo models. Cellular viability assays revealed concentration-dependent decrease survival MIA-PACA2 cells upon exposure Mito-FF (p < 0.05). Subsequent treatments prompted use several molecular analyses, including Real-time PCR, Western blot analysis, MitoSOX staining, which collectively indicated an upsurge apoptosis, concurrent reduction antioxidant enzyme expression, elevation mitochondrial ROS levels In murine xenograft model cancer, intravenous administration yielded notable tumor volume. Moreover, it upregulated expression pro-apoptotic markers, such cleaved PARP c-caspase 3, while concurrently downregulating anti-apoptotic marker, MCL-1, evidenced by analysis immunohistochemical staining It also resulted reduced enzymes like HO-1, catalase, SOD2 within excised tissues, confirmed using Cumulatively, findings underscore significant efficacy against cells, predominantly mediated through induction suppression enhancement microenvironment.

Язык: Английский

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Photostable Mn(II) Complex of Curcumin for Effective Photodynamic Therapy and Precise Three-Dimensional In Vivo Tumor Imaging

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер 17(9), С. 13660 - 13675

Опубликована: Фев. 21, 2025

Photoactive complexes of first-row transition metals with emission properties offer a dual approach to cancer treatment, enabling precise optical tumor detection and subsequent eradication using light. We report photostable photoactive mixed-ligand Mn(II) complex, Mn4, featuring naturally occurring curcumin ligand dipyridophenazine base. Mn4 demonstrates significant visible red light-triggered phototoxicity against cells imaging capability in vivo. The complex exhibits an absorption band the region, extending its tail into shows excellent dark photostability solution. induces HeLa (cervical), A549 (lung), MCF-7 (breast) (IC50 ≈ 1.0 μM), as well 3D multicellular spheroids, under low-energy (400-700 nm) red-light (660 nm). This effect is mediated by cytotoxic singlet oxygen proceeds via apoptotic mechanism. Importantly, displays significantly lower toxicity toward normal HPL1D lung HEK-293 kidney similar conditions. Cellular uptake studies reveal selective accumulation cells, mitochondrial localization, negligible BEAS-2B cells. Furthermore, demonstrated Mn4's 4T1 breast tumor-bearing vivo mouse model. In efficacy orthotopic model show that reduces volume weight dose-dependent manner blue laser (450 irradiation, highlighting potential effective photodynamic therapy (PDT) agent. Toxicological confirm does not induce abnormal biochemical or hematological parameters healthy mice. To our knowledge, this first example metal for combined PDT noninvasive imaging, paving way nonmacrocyclic Mn-based phototheranostics.

Язык: Английский

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