A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation photosensitizers (PSs), many PSs lack specific subcellular targets are limited to first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy essential for strategies. Here, we synthesized four molecules with varying benzene ring numbers thiopyrylium structures preliminarily explore their properties. The near-infrared-II (NIR-II) PS Z1, higher count, exhibited superior ROS generation mitochondria-targeting abilities, large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high (especially type-I ROS) upon 808 nm laser irradiation, leading efficient mitochondria dysfunction combined apoptosis. Moreover, they exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) photoacoustic (PAI). Furthermore, NPs-mediated effectively inhibited growth minimal adverse effects. Our findings offer promising strategy therapy, warranting further preclinical investigations PDT.

Language: Английский

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Enhancing cell pyroptosis with biomimetic nanoparticles for melanoma chemo-immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 367, P. 470 - 485

Published: Feb. 2, 2024

Language: Английский

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An Acceptor–Donor–Acceptor Structured Nano‐Aggregate for NIR‐Triggered Interventional Photoimmunotherapy of Cervical Cancer

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 3, 2024

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed dual phototherapy, including photodynamic therapy (PDT) photothermal (PTT), triggered single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), A-D-A-structured nanoaggregates exhibit broad absorption extending NIR region effectively suppressed fluorescence, which enables deep efficient conversion (η = 67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) convert ground-state oxygen (

Language: Английский

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Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Language: Английский

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Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration low drug delivery. In this study, we addressed these challenges developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced tissue permeability. CPPD1 molecule, bioconjugate hydrophobic photosensitizer strongly charged programmed death-ligand 1 (PD-L1) binding (CPP), capable self-assembling into nanoparticles an average size 199 nm in aqueous solution without need for any carriers. These carrier-free possess ability to penetrate membrane cancer cells target tumors expressing PD-L1 on their surface. Notably, effectively blocked death-1 (PD-1)/PD-L1 interactions reduced expression via lysosomal degradation. They also demonstrated responsiveness photodynamic therapy (PDT) 635 laser, leading generation ROS, induction various immunogenic deaths (ICD). Highly penetrating could immunogenically modulate microenvironment CT26 were effective treating abscopal metastatic tumors, addressing major traditional PDT.

Language: Английский

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A Second Near-Infrared Window-Responsive Metal–Organic-Framework-Based Photosensitizer for Tumor Immunotherapy via Synergistic Ferroptosis and STING Activation

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

Published: Jan. 24, 2025

Photodynamic therapy (PDT) holds promise as a cancer treatment modality due to its potential for enhanced precision and safety. To enhance deep tissue penetration minimize adsorption phototoxicity, developing photosensitizers activated by second near-infrared window (NIR-II) light shows significant potential. However, the efficacy of PDT is often impeded tumor microenvironment hypoxia, primarily caused irregular vasculature. Fortunately, stimulator interferon genes (STING) pathway, known immune activation, has been linked vasculature normalization. In this study, we developed nanoplatform (Fe-THBQ/SR) loading STING agonist (SR-717) into an iron-tetrahydroxy-1,4-benzoquinone (Fe-THBQ) metal–organic framework. Fe-THBQ was proven be effective NIR-II photosensitizer, generating numerous reactive oxygen species (ROS) under 1064 nm laser irradiation. These ROS downregulated heat shock protein expression, consequently promoting mild-photothermal (mild-PTT), facilitated ferroptosis depleting glutathione (GSH)/glutathione peroxidase 4. Moreover, Fe-THBQ/SR released SR-717 upon GSH stimulation, synergizing with ROS-mediated double-stranded DNA leakage activation. This process contributed normalization hypoxia alleviation, thereby enhancing efficacy. Overall, presented versatile single-laser-triggered mild-PTT simultaneously coupled it activation form reinforcing cycle. synergistic enhancements increased immunogenicity cells, remodeled immunosuppressive microenvironment, T lymphocyte infiltration, improved therapeutic outcomes.

Language: Английский

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Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS‐STING Pathway

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(22)

Published: May 1, 2024

Abstract The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy existing immunotherapies. Despite attempt novel immune strategies such as checkpoint inhibitors and vaccines, their effectiveness remains suboptimal due inherent difficulty in mitigating ITME simultaneously from both system. promotion anti‐tumor immunity through induction immunogenic cell death activation cGAS‐STING pathway has emerged potential counter stimulate systemic antitumor responses. Here, bimetallic polyphenol‐based nanoplatform (Mn/Fe‐Gallate nanoparticles coated with membranes is presented, MFG@TCM) which combines mild photothermal therapy (PTT) for reversing via inducing pyroptosis OS cells activating dendritic (DCs). immunostimulatory pathways, syngeneic effect, exerted substantial positive impact on promoting secretion damage‐associated molecular patterns (DAMPs) proinflammatory cytokines, favors remodeling microenvironment. Consequently, effector T led notable response, effectively inhibiting growth primary distant tumors. This study proposes new method treating using PTT mudulation, showing promise overcoming current treatment limitations.

Language: Английский

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Ternary heterostructure-driven photoinduced electron-hole separation enhanced oxidative stress for triple-negative breast cancer therapy

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 12, 2024

Abstract Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal in trigger formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, utilization ZnO NPs has been limited by shallowness short-wavelength light constrained production ROS. To overcome these limitations, a strategy involves achieving red shift towards near-infrared (NIR) spectrum, promoting separation restraining recombination electron-hole (e − -h + ) pairs. Herein, hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, multifold increase ROS generation can be achieved through following creative initiatives: (i) Au nanorods expands photocatalytic capabilities AZG into NIR domain, offering foundation NIR-induced clinical utilization; (ii) elaborate design mesoporous core-shell AZ structures facilitates redistribution pairs; (iii) incorporation GQDs structure could efficiently restrain e (iv) Modification hyaluronic acid (HA) enhance CD44 receptor mediated targeted triple-negative breast (TNBC). In addition, introduced NRs present catalysts enhancing photothermal therapy (PTT), effectively inducing apoptosis tumor cells. The resulting HA-modified (AZGH) exhibits efficient hot electron injection separation, affording unparalleled convenience enabling PDT treanment. As result, our well-designed AZGH photosensitizers exhibit excellent efficacy.

Language: Английский

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A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(39)

Published: July 8, 2024

Abstract Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation photosensitizers (PSs), many PSs lack specific subcellular targets are limited to first near‐infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep‐penetrating, organelle‐targeted pyroptosis‐mediated phototherapy essential for strategies. Here, we synthesized four molecules with varying benzene ring numbers thiopyrylium structures preliminarily explore their properties. The near‐infrared‐II (NIR‐II) PS Z1, higher count, exhibited superior ROS generation mitochondria‐targeting abilities, large Stokes shift. Through nano‐precipitation method, Z1 nanoparticles (NPs) also demonstrated high (especially type‐I ROS) upon 808 nm laser irradiation, leading efficient mitochondria dysfunction combined apoptosis. Moreover, they exceptional tumor‐targeting ability via NIR‐II fluorescence imaging (NIR‐II FI) photoacoustic (PAI). Furthermore, NPs‐mediated effectively inhibited growth minimal adverse effects. Our findings offer promising strategy therapy, warranting further preclinical investigations PDT.

Language: Английский

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Inactivated cGAS‐STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2– Breast Cancer

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Abstract Endocrine‐resistant ER+HER2– breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine‐resistant BC remain elusive. Here, analysis of the RNA‐sequencing data from patients receiving neoadjuvant endocrine therapy spatial transcriptomics both show downregulation innate immune signaling sensing cytosolic DNA, which primarily occurs in cells, not cells. Indeed, compared with endocrine‐sensitive activity DNA through cGAS‐STING pathway attenuated Screening kinase inhibitor library that this effect mainly mediated by hyperactivation AKT1 kinase, binds domain TBK1, preventing formation a trimeric complex TBK1/STING/IRF3. Notably, inactivation cGAS–STING forms positive feedback loop hyperactivated promote resistance, physiologically important clinically relevant BC. Blocking using combination an STING agonist results engagement adaptive impairs growth tumors humanized mice models, providing potential strategy for treating

Language: Английский

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