Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(9)

Published: Feb. 21, 2024

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal the photocatalyst lutetium texaphyrin (

Language: Английский

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RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(36), P. 25270 - 25281

Published: Aug. 31, 2024

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for treatment of cancer. Existing photosensitizers are predominantly engineered target diverse biomolecules, including proteins, DNA, lipids, carbohydrates, have proven greatly enhance efficacy or specificity PDT. However, it is noteworthy that there exists a conspicuous scarcity specifically designed RNAs. Recognizing crucial multifaceted roles played by RNAs in various cellular processes disease states, we ventured into development novel RNA-targeting photosensitizer, named Se-718, PDT-based cancer therapy. Se-718 been exhibit high molar absorption coefficient NIR region, which effective More importantly, demonstrated distinct capability, evidenced through rigorous testing both circular dichroism fluorescence experiments. Furthermore, shown display type I II photodynamic properties. This unique characteristic enables efficient killing cells under wide range oxygen conditions, normoxic (21% O2) hypoxic (2% O2). The IC50 can be low 100 nM, its light-to-dark toxicity ratio impressive 215 times higher, outperforming most currently available. Moreover, vivo studies conducted with tumor-bearing mice excellent antitumor effects safety profile Se-718. Considering outstanding PDT optimistic may provide innovative highly option therapeutics near future.

Language: Английский

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Multifunctional Copper‐Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(45)

Published: Sept. 17, 2024

Abstract The overexpression of polyamines in tumor cells contributes to the establishment immunosuppressive microenvironment and facilitates growth. Here, it have ingeniously designed multifunctional copper‐piceatannol/HA nanopills (Cu‐Pic/HA NPs) that effectively cause total intracellular depletion by inhibiting synthesis, depleting polyamines, impairing uptake, resulting enhanced pyroptosis cuproptosis, thus activating a powerful immune response achieve anti‐tumor therapy. Mitochondrial dysfunction from overall not only leads surge copper ions mitochondria, thereby causing aggregation toxic proteins induce but also triggers accumulation reactive oxygen species (ROS) within which further upregulates expression zDHHC5 zDHHC9 promote palmitoylation gasdermin D (GSDMD) GSDMD‐N, ultimately inducing pyroptosis. Then occurrence cuproptosis is conductive remodel microenvironment, responses growth metastasis. This therapeutic strategy through comprehensive provides novel template for cancer immunotherapy.

Language: Английский

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A panoramic perspective of recent progress in 2D and 3D covalent organic frameworks for drug delivery

Aggregate, Journal Year: 2024, Volume and Issue: 5(2)

Published: Jan. 4, 2024

Abstract The development of efficient drug delivery systems is essential for improving the efficacy and safety cancer drugs, particularly aggressive difficult‐to‐treat cancers. Covalent organic frameworks (COFs) are emerging as innovative porous nanomaterials in (DDS), due to their unique properties, including metal‐free skeleton, predetermined structures pore geometries, high porosity, large surface area, facile modification potential, good biocompatibility. These characteristics make COFs excellent candidates by enhancing loading capacity enabling precise encapsulation. This review emphasizes importance donor‐acceptor‐based COFs, which provide channels charge transportation, we also explore how π‐conjugated skeleton enhances its long‐acting fluorescent properties facilitates uptake via cell endocytosis. While this primarily focuses on recent advancements COF‐based targeted DDS, it acknowledges challenges posed diverse geometries materials discusses potential solutions. Further, underlines developing future carriers that can successfully specifically target cells, treatment efficiency while reducing adverse side effects.

Language: Английский

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Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Gasdermin (GSDM)-mediated pyroptosis involves the induction of mitochondrial damage and subsequent release DNA (mtDNA), which is anticipated to activate cGAS-STING pathway, thereby augmenting antitumor immune response. However, challenges lie in effectively triggering cancer cells subsequently enhancing activation with specificity. Herein, we developed intelligent self-cascaded pyroptosis-STING initiators cobalt fluoride (CoF2) nanocatalysts for catalytic metalloimmunotherapy. CoF2 a semiconductor structure enzyme-like activity generated substantial amount reactive oxygen species (ROS) under stimulation by endogenous H2O2 exogenous ultrasound. Importantly, discovered that Co-based nanomaterials themselves induce cells. Therefore, initially acted as inducers, caspase-1/GSDMD-dependent via Co2+ ROS, leading mtDNA release. Subsequently, were further utilized STING agonists specifically capable detecting pathway. These cascade events triggered robust response, modulating immunosuppressive tumor microenvironment into an immune-supportive state, providing favorable support therapy. This innovative strategy not only significantly impeded growth primary but also elicited response augment efficacy checkpoint inhibitors preventing distant progression. Overall, this study proposed self-cascade activating amplifying pathway specificity mediated pyroptosis, representing valuable avenue future

Language: Английский

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A Self‐Adaptive Pyroptosis Inducer: Optimizing the Catalytic Microenvironment of Nanozymes by Membrane‐Adhered Microbe Enables Potent Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(14)

Published: Dec. 28, 2023

Pyroptosis has garnered increasing attention in cancer immunotherapy. Moreover, plasma membrane damage by reactive oxygen species (ROS) is considered an effective strategy for promoting pyroptosis. However, the current tactics enhancing rupture pyroptosis are limited inherent drawbacks of ROS and immunosuppressive tumor microenvironment. Herein, a self-adaptive inducer (LPZ) designed integrating Lactobacillus rhamnosus GG (LGG) enzyme-like metal-organic framework to achieve potent LPZ can adhere cell membranes through interaction between pili LGG mucin cells. In particular, adaptive formula gradually enhance ability nanozymes produce creating acidic microenvironment anaerobic respiration. These results verify that could generate high levels both on within cells, leading pyroptotic death strong antitumor immunity. Meanwhile, eventually killed this process halt their respiration prevent potential biosafety concerns. Overall, work provides new inspiration design nanocatalytic drugs

Language: Английский

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Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(7)

Published: Nov. 5, 2023

Abstract Cancer immunotherapy has the potential to revolutionize treatment of malignant tumors, but its effectiveness is limited by low immune response rate and immune‐related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute antitumor immunity, converting “cold” tumors “hot”. Particularly, biomaterials loading pyroptosis inducers targeting tumor microenvironment engineer pyroptosis, have achieved great progress in recent years. Herein, design strategy, mechanism pathway, role induce cancer are comprehensively reviewed. The present review focuses on application biomaterials‐induced immunotherapy, including nanogel, polymer prodrug, nanovesicle, mesoporous material. Additionally, synthesis a series stimuli‐responsive nanoplatforms, glutathione‐responsive, pH‐responsive, reactive oxygen species‐responsive, enzyme‐mimicking catalytic performance, described. Meanwhile, it augments multiple processes uptake, antigen presentation, T‐cell activation, expansion. Finally, perspectives pyroptosis‐mediated inflammation break through vascular basement membrane barrier achieving efficient volcanic penetration discussed. Artificial intelligence, multi‐omics analysis, anthropogenic animal models organoids presented, aiming provide guidance assistance for constructing effective controllable pyroptosis‐engineered improving immunotherapy.

Language: Английский

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Advances in covalent organic frameworks for cancer phototherapy

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 506, P. 215720 - 215720

Published: Feb. 16, 2024

Language: Английский

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Peptide‐Driven Proton Sponge Nano‐Assembly for Imaging and Triggering Lysosome‐Regulated Immunogenic Cancer Cell Death

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 19, 2024

Abstract Triggering lysosome‐regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning “immune‐cold” tumor “hot”—a key challenge faced by cancer immunotherapies. Proton sponge such as high‐molecular‐weight branched polyethylenimine (PEI) excellent at rupturing lysosomes, but its therapeutic application hindered uncontrollable toxicity due to fixed charge density poor understanding of resulted mechanism. Here, a series proton nano‐assemblies (PSNAs) self‐assembly controllable surface cytotoxicity are created. Such PSNAs constructed via low‐molecular‐weight PEI covalently bound self‐assembling peptides carrying tetraphenylethene pyridinium (PyTPE, aggregation‐induced emission‐based luminogen). Assembly assisted the peptide‐PyTPE leads enhanced positive charges PSNA. The tendency further optimized tuning hydrophilic hydrophobic components within peptide, thus resulting in PSNA highest fluorescence, density, uptake, cytotoxicity. Systematic mechanistic studies reveal that lysosome rupturing‐regulated necroptosis least two causes death. Tumor cells undergoing PSNA‐triggered ICD activate immune cells, suggesting great potential trigger anticancer immunity.

Language: Английский

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A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 16967 - 16981

Published: June 18, 2024

Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration immunotherapy. Here, we report cascade-amplified inducer CSCCPT/SNAP that utilizes reactive nitrogen species (RNS), self-supplied from diffusion-controlled reaction between oxygen (ROS) and nitric oxide (NO) to potentiate immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin NO initiate pyroptosis. Mechanistically, cascade amplification antitumor immune response is prompted cooperation enhanced RNS with long lifetime, which could be used as trigger effectively compensate inherent drawbacks ROS, resulting in long-lasting favoring Tumor growth efficiently inhibited mouse melanoma tumors through facilitation oxygen/nitrogen (RONS)-NO synergy. In summary, our therapeutic approach supramolecular engineering nanotechnology integrate producers donors tumor-specific stimulus responses into system guarantees synchronous these two elicit pyroptosis-evoked response, using amplifier. RONS-NO synergy achieves sustained robust cancer

Language: Английский

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