Nitric Oxide-Producing Multiple Functional Nanoparticle Remodeling Tumor Microenvironment for Synergistic Photodynamic Immunotherapy against Hypoxic Tumor

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

Published: Feb. 6, 2025

The treatment of pancreatic cancer faces significant challenges due to connective tissue hyperplasia and severe hypoxia. Unlike oxygen-dependent Type II photosensitizers, I photosensitizers can produce a substantial amount reactive oxygen species, even under hypoxic conditions, making them more suitable for photodynamic therapy cancer. However, the dense extracellular matrix limits penetration efficiency presence immunosuppressive cells in tumor microenvironment reduces therapeutic effect. To address these challenges, we designed photoimmunotherapeutic M1@PAP nanoparticles composed photosensitizer anti-PD-L1 siRNA (siPD-L1), which was encapsulated into M1 macrophage membrane vesicles. In this system, pyropheophorbide-a (PPA) covalently conjugated poly-l-arginine (Arg9). Notably, it capable generating sufficient superoxide anions thereby functioning as photosensitizer. Furthermore, Arg9 acted nitric oxide (NO) donor, enhancing nanophotosensitizer by inhibiting cancer-associated fibroblast (CAF) activation decomposing matrix. Additionally, vesicles provided active targeting capabilities reeducated immunosuppressed M2 macrophages. reversal further promoted efficacy immunotherapy, showing great potential synergistic immunotherapy against tumor.

Language: Английский

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Fluorinated Cyclodextrin Supramolecular Nanoassembly Enables Oxygen-Enriched and Targeted Photodynamic Therapy

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

Published: March 8, 2025

Photodynamic therapy has become a promising treatment modality against many diseases, but its dilemma―the intrinsic hypoxia of solid tumors and the high oxygen dependence for generation cytotoxic species―has seriously hampered practical translation. Herein binary supramolecular nanocarrier, which is composed fluorocarbon chain-appended β-cyclodextrin as an carrier adamantane-grafted hyaluronic acid cell-targeting agent, can deliver different types photosensitizers by multiple noncovalent interactions. Superior to alkylated counterpart, fluorinated amphiphilic spontaneously form nanoparticulate assembly exhibit oxygen-enrichment performance. The obtained nanoassembly alleviate in tumor microenvironment enhance efficacy photodynamic therapy. Remarkable phototoxicity minimal dark toxicity are observed cancer cells, meanwhile, preferential accumulation significant ablation realized tumor-bearing mice. To be envisioned, this capable efficiently carrying explored universal platform precise phototherapeutics.

Language: Английский

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Intrinsic stimuli-responsive main-chain supramolecular polymers driven by dative B←N bonds

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A novel main-chain supramolecular polymer (MCSP) with intrinsic stimuli-responsiveness based on dative B ← N bonds has been successfully developed.

Language: Английский

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Enhanced efficiency and selectivity in reactive oxygen species generation using thiazolo[5,4-d]thiazole-based supramolecular photosensitizers

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Language: Английский

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Cascade Responsive Photosensitizer for Precise Delivery and Photodynamic Therapy

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

We report a tumor microenvironment-responsive photosensitizer (1) as molecular chameleon with cascade transformation capabilities for precision-controlled delivery. 1 is encapsulated in pH-responsive surfactant to form 1a PEGylated surface that does not generate ROS normal tissues. The generation activated by the overexpressed glutathione at acidic site yield 2 through an aromatic nucleophilic substitution. This of hydrophobic hydrophilic leads release size reduction, potentially enhancing drug accumulation and facilitating penetration. Furthermore, after treatment, deactivated γ-glutamyl transferase specific hydrolysis intramolecular rearrangement reactions, thereby reducing potential undesired phototoxicity. In vitro vivo studies show affords excellent phototoxicity cancer cells pyroptosis pathway. work offers promising strategy design chameleons control spatiotemporal delivery photosensitizes enhance photodynamic therapy efficacy.

Language: Английский

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Superimposed Effect of Intramolecular Modular Assembling and Silver Coordination to Amplify Superoxide Anion Radical for Antitumor and Antibacterial Photodynamic therapy

ACS Materials Letters, Journal Year: 2025, Volume and Issue: unknown, P. 1887 - 1895

Published: April 16, 2025

Language: Английский

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Multifunctional Fluorescent Probes for Profiling Cys, Hcy, GSH, and SO₂: Illuminating Their Dynamics in Apoptosis and Ferroptosis

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: May 3, 2025

Abstract The ability to perform simultaneous fluorescence imaging of multiple targets is essential, providing crucial multi‐parametric information necessary for understanding complex biological interactions and processes. In this study, TBC , a novel multi‐signal fluorescent probe presented, crafted differentiation in situ real‐time monitoring homocysteine (Hcy), cysteine (Cys), sulfur dioxide (SO 2 ), glutathione (GSH), illuminating the dynamic metabolic status endogenous reactive species. achieves an ultrahigh signal‐to‐background ratio, enabling wash‐free direct dynamics distribution these entities living cells zebrafish. Notably, has revealed distinctive features Hcy/Cys/SO /GSH during apoptosis ferroptosis. This innovative acts as key tool unraveling conversion networks species assessing impact oscillations programmed cell death progression diverse diseases, effectively uncovering concurrent biochemical various settings events.

Language: Английский

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Conjugated Polymer-Photosensitizers for Cancer Photodynamic Therapy and Their Multimodal Treatment Strategies

Polymers, Journal Year: 2025, Volume and Issue: 17(9), P. 1258 - 1258

Published: May 5, 2025

Conjugated polymers (CPs) have emerged as promising candidates for photodynamic therapy (PDT) in cancer treatment due to their high fluorescence quantum yield, excellent photostability, and remarkable reactive oxygen species (ROS) generation capability. This review systematically summarizes molecular design strategies augment CP photosensitivity efficiency, including: (1) constructing donor–acceptor (D-A) alternating structures, (2) incorporating aggregation-induced emission (AIE) moieties, (3) employing heavy-atom effects, (4) designing hyperbranched architectures. In addition, considering the limitations of monotherapy like tumor heterogeneity, we will further discuss synergistic CP-mediated PDT combination with other therapeutic modalities, including photothermal (PTT)-PDT, immunotherapy-PDT, chemotherapy-PDT, Chemiluminescence (CL)-PDT, diagnostic technology-PDT, chemodynamic (CDT)-PDT. These multimodal approaches leverage complementary mechanisms achieve enhanced eradication efficacy.

Language: Английский

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Enhanced ferroptosis in triple-negative cancer cells achieved by a type-I cell membrane-targeted tetrabenzophenazine photosensitizer

Sensors and Actuators B Chemical, Journal Year: 2025, Volume and Issue: unknown, P. 137978 - 137978

Published: May 1, 2025

Language: Английский

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Fully Conjugated Thiophene-Fused Oligo-BODIPYs: A Class of Intensely Near-Infrared Absorbing, Arc-Shaped Materials with up to 31 Linearly-Fused Rings

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

Published: May 28, 2025

Structurally well-defined large π-conjugated systems attract significant interest in molecular materials both for their unique electronic/photophysical properties and unexplored structure-property relationships arising from synthetic challenges. Herein, we address this challenge by leveraging a series of polycondensed π-system doping with B, N S heteroatoms. In our approach, fully conjugated thiophene-fused oligo-BODIPYs atomic precision have been efficiently synthesized through the combination intermolecular SNAr reactions followed intramolecular aromatic oxidative couplings halogenated BODIPY precursors. The largest architecture is fused octamer, featuring coplanar backbone 31 linearly rings. extended π-conjugation causes dramatic shift absorption event about 500 nm (monomer) to 822 (octamer) extremely high molar absorptivities reaching 800,000 M-1 cm-1, as well maintaining intense fluorescence intensity (ΦFL up 0.32), long triplet lifetime (τT = 0.61-15.4 μs), efficient quantum yields (ΦT 0.24-0.81) good singlet oxygen generation abilities. More interestingly, due weak aromaticity thiophene, exhibit state localization conjugation length increases, where energy remains constant while decreases significantly. Notably, near-infrared thermally activated delayed (TADF) observed even tetramers, hexamers, octamers. Our findings not only present new heteroatom-doped condensed π-systems but also establish precise regulation mechanism singlet-triplet levels molecules rigid structures. Furthermore, work provides novel strategy designing next-generation TADF narrowband emission.

Language: Английский

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