Anti‐Quenching NIR‐II J‐Aggregates of Benzo[c]thiophene Fluorophore for Highly Efficient Bioimaging and Phototheranostics

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(20)

Published: March 3, 2023

Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used construct long-wavelength NIR-II emitters as optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, wide applications in fluorescence imaging impeded by limited varieties of J-type backbone serious quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) anti-quenching effect is reported highly efficient phototheranostics. The BT manipulated have Stokes shift over 400 nm aggregation-induced (AIE) property conquering self-quenching issue fluorophores. Upon BT6 assemblies an aqueous environment, absorption 800 1000 boosted more than 41 26 folds, respectively. In vivo visualization whole-body blood vessel imaging-guided phototherapy results verify that NPs agent cancer This work develops strategy precisely properties biomedical applications.

Language: Английский

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A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 25, 2023

Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) hypoxia-responsive prodrug multifunctional combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence photoacoustic (PA) brightness the strong light absorption ability, as well amplified type I II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating high-performance paclitaxel (PTX) into nanoparticles, further camouflaging macrophage cell membrane, tumor-targeting theranostic agent is built. integration of PA imaging helps to delineate tumor site sensitively, providing accurate guidance light-induced PDT effect could consume local oxygen lead severer hypoxia, accelerating release PTX drug. As result, chemotherapy induces immunogenic death, which not only elicit antitumor immunity suppress primary tumor, but also inhibit growth distant in 4T1 tumor-bearing female mice. strategy develop agents rational molecular design boosting

Language: Английский

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Aggregation‐induced emission luminogens for in vivo molecular imaging and theranostics in cancer

Aggregate, Journal Year: 2023, Volume and Issue: 4(5)

Published: May 6, 2023

Abstract Cancer is one of the most fatal diseases for decades. Aggregation‐induced emission luminogens (AIEgens) have been recently used as molecular imaging or therapeutic agents in cancers, due to advantages large Stokes shift, high quantum yield, great biocompatibility, and strong photostability. AIEgens can specifically target different types cancer via diverse targeting strategies. AIEgen‐based fluorescence imaging, especially near‐infrared demonstrated deep penetration suitable signal‐to‐noise ratio, which allows reliable vivo imaging. Combined with other modalities, multimodal could provide multidimensional hallmarks from perspectives. In addition, phototherapy be photodynamic therapy photothermal therapy, facilitate ablation cells good biosafety effects vivo. nanoparticles fabricated some specific chemicals, drugs, siRNA, display synergistic cancers. This paper comprehensively describes current status future perspectives AIEgens, showed a potential preclinical clinical translation on theranostics cancer.

Language: Английский

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A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 2, 2023

Abstract Lack of sufficient cytotoxic T lymphocytes (CD8 + cells) infiltration and dysfunctional state CD8 cells are considered enormous obstacles to antitumor immunity. Herein, we construct a synergistic nanoplatform promote cell in tumors while restoring function by regulating methionine metabolism activating the STING innate immune pathway. The CRISPR/Cas9 system down-regulates transporter SLC43A2 restricts uptake tumor cells, thereby relieving competition pressure cells; simultaneously, released nutrition metal ions activate cGAS/STING In this work, described can enhance effect immunotherapy preclinical cancer models female mice, enhancing pathway mediated immunity facilitating development amino acid metabolic intervention-based therapy.

Language: Английский

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Bioorthogonal Guided Activation of cGAS‐STING by AIE Photosensitizer Nanoparticles for Targeted Tumor Therapy and Imaging

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(52)

Published: Sept. 5, 2023

Abstract Photodynamic therapy (PDT) and photothermal (PTT) leverage reactive oxygen species (ROS) control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria nucleus, activating the cGAS‐STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered limitations such as suboptimal tumor targeting, aggregation‐caused quenching (ACQ), restricted excitation emission wavelengths. Here, this work designs novel nanoparticles based on aggregation‐induced (AIE) (BODTPE) for targeted near‐infrared II fluorescence imaging (NIR‐II FLI) with enhanced PDT/PTT effects. BODTPE is employed a monomer, dibenzocyclooctyne (DBCO)‐PEG 2k ‐amine serving an end‐capping polymer, synthesize BODTPE‐containing polymer (DBD). Further, through self‐assembly, DBD mPEG‐DSPE combined form (NP‐DBD). Notably, DBCO surface of NP‐DBD can react azide groups cancer cells pretreated Ac 4 ManNAz copper‐free click reaction. This innovative formulation led accumulation within sites, phenomenon convincingly demonstrated murine models subjected N ‐azidoacetylmannosamine‐tetraacylated (Ac ManNAz) pretreatment. Significantly, exhibits multifaceted effect encompassing PDT/PTT/NIR‐II FLI upon 808 nm laser irradiation, thereby better culminating compelling inhibition augmented robust modulation.

Language: Английский

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Immuno-photodynamic Therapy (IPDT): Organic Photosensitizers and Their Application in Cancer Ablation

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 682 - 699

Published: Feb. 14, 2023

Photosensitizer-based photodynamic therapy (PDT) has been considered as a promising modality for fighting diverse types of cancers. PDT directly inhibits local tumors by minimally invasive strategy, but it seems to be incapable achieving complete eradication and fails prevent metastasis recurrence. Recently, increasing events proved that was associated with immunotherapy triggering immunogenic cell death (ICD). Upon specific wavelength light irradiation, the photosensitizers will turn surrounding oxygen molecules into cytotoxic reactive species (ROS) killing cancer cells. Simultaneously, dying tumor cells release tumor-associated antigens, which could improve immunogenicity activate immune However, progressively enhanced immunity is typically limited intrinsic immunosuppressive microenvironment (TME). To overcome this obstacle, immuno-photodynamic (IPDT) come one most beneficial strategies, takes advantage stimulate response unite inducing immune-OFF immune-ON ones, achieve systemic In Perspective, we provide review recent advances in organic photosensitizer-based IPDT. The general process responses triggered (PSs) how enhance antitumor pathway modifying chemical structure or conjugating targeting component discussed. addition, future perspectives challenges IPDT strategies are also We hope Perspective inspire more innovative ideas executable developments war against cancer.

Language: Английский

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A Microenvironment Dual‐Responsive Nano‐Drug Equipped with PD‐L1 Blocking Peptide Triggers Immunogenic Pyroptosis for Prostate Cancer Self‐Synergistic Immunotherapy

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(16)

Published: Jan. 25, 2023

Abstract Induction of immunogenic cell death (ICD) in tumor combined with immune checkpoint blockade (ICB) therapy is widely developed to improve the efficacy cancer immunotherapy. However, current ICD induced based on apoptosis, i.e., often restricted immunogenicity owing inflammatory quenching that occurs early apoptosis. Recently, pyroptosis demonstrated be a more efficient form, pyroptosis. The contents released during can powerfully activate immunogenicity. Herein, first, it lower doses epigenetic drug decitabine increase GSDME expression prostate (PCa) RM‐1 cells and successfully induce an apoptosis‐pyroptosis transition after photodynamic (PDT). Subsequently, microenvironment dual‐responsive nano‐drug equipped PD‐L1 blocking peptide (TSD@LSN‐D) for self‐synergistic poorly PCa model confirm powerful antitumor response evoked by TSD@LSN‐D not only effectively inhibit primary but also form long‐term memory prevent recurrence metastasis. To best authors’ knowledge, this work presents first concept promotes apoptosis–pyroptosis PDT through modulation. Furthermore, combination ICB opens new platform

Language: Английский

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Single Atom Catalysts Remodel Tumor Microenvironment for Augmented Sonodynamic Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: March 16, 2024

The immunosuppressive tumor microenvironment (TME) is a huge hurdle in immunotherapy. Sono-immunotherapy new treatment modality that can reverse TME, but the sonodynamic effects are compromised by overexpressed glutathione (GSH) and hypoxia TME. Herein, this work reports sono-immunotherapy strategy using Pd

Language: Английский

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Cell Membrane as A Promising Therapeutic Target: From Materials Design to Biomedical Applications

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: Feb. 19, 2024

The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction information exchange. Therefore, disrupting its structure or impairing functions can potentially cause irreversible damage. Presently, the tumor recognized as promising therapeutic target for various treatment methods. Given extensive research focused on membranes, it both necessary timely to discuss these developments, from materials design specific biomedical applications. This review covers treatments based functional targeting membrane, ranging well-known membrane-anchoring photodynamic therapy recent lysosome-targeting chimaeras protein degradation. diverse mechanisms are introduced in following sections: phototherapy, self-assembly situ biosynthesis degradation proteins by chimeras. In each section, we outline conceptual general derived numerous studies, emphasizing representative examples understand advancements draw inspiration. Finally, some challenges future directions membrane-targeted our perspective. aims engage multidisciplinary readers encourage researchers related fields advance fundamental theories practical applications membrane-targeting agents.

Language: Английский

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Exosome‐Inhibiting Polymeric Sonosensitizer for Tumor‐Specific Sonodynamic Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: March 6, 2024

Combination cancer immunotherapy based on electromagnetic energy and shows potent anti-cancer efficacy. However, as a factor that mediates tumor metastasis immune suppression, the impact of exosomes therapy under stimulation remains unclear. Herein, findings indicate sonodynamic (SDT) increases serum exosome levels by inducing apoptotic loosening extracellular matrix, promoting lung metastasis. To address this problem, an exosome-inhibiting polymeric sonosensitizer (EIPS) selectively inhibiting generation in response to biomarker is synthesized. EIPS consists semiconducting polymer backbone capable SDT poly(ethylene glycol) layer conjugated with tumor-specific enzyme-responsive inhibitor prodrug. After being cleaved Cathepsin B, releases active inhibitors, preventing exosome-mediated suppression As result, elicits robust antitumor effects through synergistic effect inhibition, completely establishing long-term memory effect. This first example showing combining inhibition can elicit without help typical agonists.

Language: Английский

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