Metallodrugs in cancer nanomedicine

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(7), P. 2544 - 2582

Published: Jan. 1, 2022

Metal complexes are extensively used for cancer therapy. The multiple variables available tuning (metal, ligand, and metal-ligand interaction) offer unique opportunities drug design, have led to a vast portfolio of metallodrugs that can display higher diversity functions mechanisms action with respect pure organic structures. Clinically approved metallodrugs, such as cisplatin, carboplatin oxaliplatin, treat many types play prominent roles in combination regimens, including immunotherapy. However, generally suffer from poor pharmacokinetics, low levels target site accumulation, metal-mediated off-target reactivity development resistance, which all limit their efficacy clinical translation. Nanomedicine has arisen powerful tool help overcome these shortcomings. Several nanoformulations already significantly improved the reduced toxicity (chemo-)therapeutic drugs, some promising metallodrug-containing nanomedicines currently trials. In this critical review, we analyse challenges assess advantages limitations metallodrug delivery, both nanocarrier metal-nano interaction perspective. We describe latest most relevant nanomedicine formulations developed metal complexes, discuss how rational coordination chemistry technology assist promoting translation metallodrugs.

Language: Английский

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In‐vitro and In‐vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(17), P. 9474 - 9479

Published: Jan. 15, 2021

Abstract Photocatalytic anticancer profile of a Ir III photocatalyst ( Ir3 ) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported. showed selective photo‐cytotoxicity against cisplatin‐ sorafenib‐resistant cell lines while remaining dormant to normal in the dark. exhibited photo‐catalytic oxidation cellular co‐enzyme, reduced nicotinamide adenine dinucleotide phosphate (NADPH), amino acids via single electron transfer mechanism. The photo‐induced intracellular redox imbalance change mitochondrial membrane potential resulted necrosis apoptosis cancer cells. Importantly, efficiency as evident from vivo zebrafish mouse models. To best our knowledge, first based such photocatalytic therapeutic effect.

Language: Английский

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ROS-based dynamic therapy synergy with modulating tumor cell-microenvironment mediated by inorganic nanomedicine

Coordination Chemistry Reviews, Journal Year: 2021, Volume and Issue: 437, P. 213828 - 213828

Published: March 9, 2021

Language: Английский

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Enzyme Mimics for Engineered Biomimetic Cascade Nanoreactors: Mechanism, Applications, and Prospects

Advanced Functional Materials, Journal Year: 2021, Volume and Issue: 31(50)

Published: Sept. 8, 2021

Abstract Multiple enzyme‐driven biological catalytic cascades occur in living organisms, guiding highly efficient and selective transformations of substrates. Inspired by the merits these cascade systems, enormous efforts have been devoted to developing novel systems mimic reactions over past few years. Nanozymes, a class enzyme mimics, are nanomaterials with enzyme‐like activity. The emergence development nanozymes has significantly advanced biomimetic nanoreactors. Currently, nanoreactors driven widely used exhibit many advantages such as superior efficiency high stability, resulting significant advancements biosensing biomedical applications. latest advances understanding mechanism nanozyme‐engineered their progressive applications for comprehensively covered here. First, nanozyme enzyme/nanozyme‐engineered categorized according properties. Then, applications, including cancer therapy, antibacterial activity, antioxidation, hyperuricemia therapy covered. conclusion describes most important challenges opportunities remaining this exciting area research.

Language: Английский

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Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 11, 2022

Abstract Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to existence blood-brain barrier (BBB) and difficulty maintain an effective drug accumulation in deep GBM lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation achieve BBB crossing tumor penetration drugs. Synthesized crosslinking pullulan poly(deca-4,6-diynedioic acid) (PDDA) loaded with temozolomide indocyanine green (ICG), nanogels are inert endogenous oxidative conditions but selectively disintegrated ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation active targeting. The controlled on lesions excites ICG deforms cumulated trigger burst release for facilitated permeation infiltration into distal cells. These NIR-activatable suppress growth orthotopic stem cells-bearing mouse models significantly extended survival.

Language: Английский

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State of the art advancements in sonodynamic therapy (SDT): Metal-Organic frameworks for SDT

Chemical Engineering Journal, Journal Year: 2022, Volume and Issue: 449, P. 137889 - 137889

Published: July 4, 2022

Language: Английский

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Engineering lactate-modulating nanomedicines for cancer therapy

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(3), P. 973 - 1000

Published: Jan. 1, 2023

Lactate in tumors has long been considered "metabolic junk" derived from the glycolysis of cancer cells and utilized only as a biomarker malignancy, but is presently believed to be pivotal regulator tumor development, maintenance metastasis. Indeed, lactate can "fuel" for energy supply functions signaling molecule, which actively contributes progression, angiogenesis, immunosuppression, therapeutic resistance, etc., thus providing promising opportunities treatment. However, current approaches regulating homeostasis with available agents are still challenging, mainly due short half-life, low bioavailability poor specificity these their unsatisfactory outcomes. In recent years, modulation nanomedicines have emerged charming efficient strategy fighting cancer, play important roles optimizing delivery lactate-modulating more precise effective Integrating specific diverse may overcome intrinsic restrictions different modalities by remodeling pathological microenvironment achieving enhanced therapy. this review, most advances engineering functional that modulate therapy summarized discussed, fundamental mechanisms benefits various therapeutics elucidated. Finally, challenges perspectives emerging anti-tumor field highlighted.

Language: Английский

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Mn-based cGAS-STING activation for tumor therapy

Chinese Journal of Cancer Research, Journal Year: 2023, Volume and Issue: 35(1), P. 19 - 43

Published: Jan. 1, 2023

Immunotherapy has efficiently revolutionized the treatment of human neoplastic diseases. However, overall responsive rate current immunotherapy is still unsatisfactory, benefiting only a small proportion patients. Therefore, significant attention been paid to modulation tumor microenvironment (TME) for enhancement immunotherapy. Interestingly, recent studies have shown that cyclic GMP-AMP synthase-stimulator interferon gene (cGAS-STING) was initially found as an innate immune sensor recognize cytoplasmic DNA (such bacterial, viral, micronuclei, and mitochondrial). It promising signaling pathway activate antitumor responses via type I production. Notably, Mn2+ be critical molecule sensitize activation cGAS-STING better This led development Mn2+-based strategies pathway. In this review, we aimed summarize progress field, focusing on following three aspects. First, briefly introduced activation, its regulation effect immunity cycle discussed. Along with this, several agonists were their potential immunotherapeutic drugs. Then, basic biological functions illustrated, roles in activation. Next, systematically reviewed immunotherapy, which can classified by methods based alone or combined other therapeutic modalities. We finally speculated future perspectives field provided rational suggestions develop therapeutics.

Language: Английский

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De Novo Designed Ru(II) Metallacycle as a Microenvironment‐Adaptive Sonosensitizer and Sonocatalyst for Multidrug‐Resistant Biofilms Eradication

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(15)

Published: Feb. 8, 2024

Abstract Albeit sonodynamic therapy (SDT) has achieved encouraging progress in microbial sterilization, the scarcity of guidelines for designing highly effective sonosensitizers and intricate biofilm microenvironment (BME), substantially hamper therapeutic efficacy against infections. To address bottlenecks, we innovatively design a Ru(II) metallacycle‐based sonosensitizer/sonocatalyst (named Ru‐A3‐TTD ) to enhance potency sonotherapy by employing molecular engineering strategies tailored BME. Our approach involves augmenting ’s production ultrasonic‐triggered reactive oxygen species (ROS), surpassing performance commercial sonosensitizers, through straightforward but potent π‐expansion approach. Within BME, synergistically amplifies sonotherapeutic via triple‐modulated approaches: (i) alleviation hypoxia, leading increased ROS generation, (ii) disruption antioxidant defense system, which shields from glutathione consumption, (iii) enhanced penetration, enabling deep sites. Notably, sono‐catalytically oxidizes NADPH, critical coenzyme involved defenses. Consequently, demonstrates superior eradication multidrug‐resistant Escherichia coli compared conventional clinical antibiotics, both vitro vivo. our knowledge, this study represents pioneering instance supramolecular sonosensitizer/sonocatalyst. It provides valuable insights into structure‐activity relationship paves promising pathway treatment

Language: Английский

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Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(21), P. 13910 - 13923

Published: May 16, 2024

Thanks to their excellent photoelectric characteristics generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present H2O2-driven black mesoporous nanomotor near-infrared (NIR) light absorption capability autonomous navigation ability, which effectively enhances NIR light-triggered PDT. The was rationally designed fabricated based on Janus nanostructure, consists light-responsive nanosphere an enzyme-modified periodic organosilica (PMO) nanorod that wraps around nanosphere. overexpressed H2O2 can drive TME catalysis catalase PMO domain. By precisely controlling ratio compartments TiO2&PMO nanomotors achieve optimal self-propulsive directionality velocity, enhancing cellular uptake facilitating deep penetration. Additionally, by decomposition endogenous within tumors, these continuously supply enable highly efficient ROS production photocatalysis TiO2, leading intensified effects effective inhibition.

Language: Английский

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