Theranostic Fluorescent Probes

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(5), P. 2699 - 2804

Published: Feb. 29, 2024

The ability to gain spatiotemporal information, and in some cases achieve control, the context of drug delivery makes theranostic fluorescent probes an attractive intensely investigated research topic. This interest is reflected steep rise publications on topic that have appeared over past decade. Theranostic probes, their various incarnations, generally comprise a fluorophore linked masked drug, which released as result certain stimuli, with both intrinsic extrinsic stimuli being reported. release then signaled by emergence signal. Importantly, use appropriate fluorophores has enabled not only this emerging fluorescence marker for but also provided modalities useful photodynamic, photothermal, sonodynamic therapeutic applications. In review we highlight recent work particular focus are activated tumor microenvironments. We summarize efforts develop other applications, such neurodegenerative diseases antibacterials. celebrates diversity designs reported date, from discrete small-molecule systems nanomaterials. Our aim provide insights into potential clinical impact still-emerging direction.

Language: Английский

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Genetically Engineering Cell Membrane‐Coated BTO Nanoparticles for MMP2‐Activated Piezocatalysis‐Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(18)

Published: Feb. 21, 2023

Tumor immunotherapy based on immune checkpoint blockade (ICB) still suffers from low host response rate and non-specific distribution of inhibitors, greatly compromising the therapeutic efficiency. Herein, cellular membrane stably expressing matrix metallopeptidase 2 (MMP2)-activated PD-L1 blockades is engineered to coat ultrasmall barium titanate (BTO) nanoparticle for overcoming immunosuppressive microenvironment tumors. The resulting M@BTO NPs can significantly promote BTO's tumor accumulation, while masking domains antibodies are cleaved when exposure MMP2 highly expressed in tumor. With ultrasound (US) irradiation, simultaneously generate reactive oxygen species (ROS) O2 BTO mediated piezocatalysis water splitting, promoting intratumoral infiltration cytotoxic T lymphocytes (CTLs) improving therapy tumor, effective growth inhibition lung metastasis suppression a melanoma mouse model. This nanoplatform combines MMP2-activated genetic editing cell with US responsive both stimulation specific inhibition, providing safe robust strategy enhancing against

Language: Английский

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Molecular substrates for the construction of afterglow imaging probes in disease diagnosis and treatment

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(14), P. 4549 - 4566

Published: Jan. 1, 2023

This tutorial review introduces recent advances in molecular afterglow imaging using organic materials with a focus on substrates, mechanisms, design principles of probes, and their biomedical applications.

Language: Английский

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Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8991 - 9003

Published: March 21, 2024

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as first example Ru(II) supramolecular ICD inducer. synergistically potentiates immunomodulatory and reduces adverse through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting tumor cells, precision organelle localization, improved penetration/retention capabilities. Specifically, demonstrates excellent depth-activated ROS production (∼1 cm), resistance to diffusion, anti-ROS quenching. Moreover, exhibits promising results cellular uptake generation cancer cells multicellular spheroids. Importantly, induces more efficient an ultralow dose (10 μM) compared conventional agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency inducer, eliciting CD8+ T depleting Foxp3+ effects. Our research lays foundation for design secure exceptionally potent metal-based agents immunotherapy.

Language: Английский

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Expanded ROS Generation and Hypoxia Reversal: Excipient‐free Self‐assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(30)

Published: May 12, 2024

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This discovers that hydrophobic interaction forces between ICG 17-DMAG promote photostability its intersystem crossing (ISC) process, thereby improving ROS quantum yield from 0.112 to 0.46. Augmented enhances PDT further immunogenic cell death (ICD) effects. inhibits HSP90/hypoxia-inducible factor 1α (HIF-1α) axis dramatically reverse immunosuppressive tumor microenvironment caused PDT-aggravated hypoxia. In mouse model pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration MHC I II activation, demonstrating superior ICD effects in situ powerful systematic antitumor immunity generation, eventually achieving vigorous recurrence resistance. study proposes an unsophisticated versatile strategy for enhancing systemic potentially extending it multiple cancers.

Language: Английский

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Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 10, 2024

Abstract Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of tumor itself is a serious obstacle to efficacy. Here, this work reports strategy enhance PCa by triggering cascade self‐enhanced ferroptosis in cells, turning from “hot”. This develops transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness glutathione peroxidase 4 (GPX4) protein targeting. self‐assembles into nanoparticles under aqueous conditions transforms nanofibers response ALP during endosome/lysosome uptake promoting lysosomal membrane permeabilization (LMP). On one hand, released TEP‐FFG‐CRAY target GPX4 selectively degrade light irradiation, inducing ferroptosis; on other large amount leaked Fe 2+ further amplify through Fenton reaction. TEP‐FFG‐CRApY‐induced improves cell maturation dendritic cells (DCs) increasing intratumor T‐cell infiltration. More importantly, recovered T secreting amounts interferon‐gamma (IFN‐γ). provides novel molecular design synergistic molecularly targeted therapy tumors.

Language: Английский

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Boosting Theranostic Performance of AIEgens Using Nanocatalyzer for Robust Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(23)

Published: Feb. 15, 2024

Abstract High‐performance theranostic systems are of paramount importance for achieving precise image‐guided cancer immunotherapy. Here, a novel nanoplatform is presented that integrates aggregation‐induced emission luminogen (AIEgen) with prussian blue (PB) nanocatalyzer robust The AIEgen dimethylamine substitution demonstrates compelling near‐infrared (NIR) light‐induced photothermal conversion and photodynamic therapy (PDT) capabilities. By incorporating into porous PBNPs, further enveloped within M1 macrophage membrane, tumor‐specific nanoagent constructed. This strategic integration effectively constrains the molecular motion AIEgen, leading to amplified NIR‐II fluorescence brightness PDT attributes. Moreover, PBNPs can catalyze tumor‐overexpressed H 2 O generate oxygen boost efficacy, PB's NIR absorption also intensifies photoacoustic imaging effect. provides comprehensive information photoimmunotherapy in orthotopic breast cancer‐bearing mice. Leveraging its potent immunogenic cell death effect, not only significantly inhibits growth, but generates whole‐cell therapeutic vaccine protect mice from tumor rechallenge. In highly malignant post‐surgery models, enables both accurate identification residual tumors efficient inhibition postoperative recurrence pulmonary metastasis. study will offer valuable insights creating efficacious multifaceted protocols.

Language: Английский

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Noninvasive Imaging of Tumor Glycolysis and Chemotherapeutic Resistance via De Novo Design of Molecular Afterglow Scaffold

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24386 - 24400

Published: Oct. 26, 2023

Chemotherapeutic resistance poses a significant challenge in cancer treatment, resulting the reduced efficacy of standard chemotherapeutic agents. Abnormal metabolism, particularly increased anaerobic glycolysis, has been identified as major contributing factor to resistance. To address this issue, noninvasive imaging techniques capable visualizing tumor glycolysis are crucial. However, currently available methods (such PET, MRI, and fluorescence) possess limitations terms sensitivity, safety, dynamic capability, autofluorescence. Here, we present de novo design unique afterglow molecular scaffold based on hemicyanine rhodamine dyes, which holds promise for low-background optical imaging. In contrast previous designs, exhibits responsive "OFF-ON" signals through spirocyclization, thus enabling simultaneous control photodynamic effects luminescence efficacy. This leads larger range, broader detection higher signal enhancement ratio, sensitivity. Furthermore, integration multiple functionalities simplifies probe design, eliminates need spectral overlap, enhances reliability. Moreover, have expanded applications by developing various probes different targets. Notably, developed water-soluble pH-responsive nanoprobe living mice. monitors glycolytic inhibitors or oxidative phosphorylation providing valuable tool evaluating cell sensitivity these inhibitors. Therefore, new presents promising approach understanding monitoring resistance, guiding precision medicine future.

Language: Английский

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Activatable Sonoafterglow Nanoprobes for T‐Cell Imaging

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(30)

Published: April 19, 2023

Real-time imaging of immune systems benefits early diagnosis disease and precision immunotherapy; however, most existing probes either have "always-on" signals with poor correlation to responses, or rely on light excitation limited depth. In this work, an ultrasound-induced afterglow (sonoafterglow) nanoprobe is developed specifically detect granzyme B for accurate T-cell immunoactivation in vivo. The sonoafterglow (Q-SNAP) consists sonosensitizers, substrates, quenchers. Upon ultrasound irradiation, sonosensitizers generate singlet oxygen, which converts substrates high-energy dioxetane intermediates that slowly release energy after cessation. Due the proximity, from can be transferred quenchers, leading quenching. Only presence B, quenchers are liberated Q-SNAP, resulting bright emission a limit detection (LOD, 2.1 nm) much lower than fluorescent probes. deep-tissue-penetrating ultrasound, induced through tissue 4 cm thickness. Based between Q-SNAP not only distinguishes autoimmune hepatitis healthy liver as h probe injection, but also effectively monitors cyclosporin-A-mediated reversal hyperactivation. thus offers possibilities dynamic monitoring dysfunction evaluation prophylactic immunotherapy deep-seated lesions.

Language: Английский

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A Bright Two‐Photon Lipid Droplets Probe with Viscosity‐Enhanced Solvatochromic Emission for Visualizing Lipid Metabolic Disorders in Deep Tissues

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(35)

Published: May 8, 2023

Abstract The polarity of lipid droplets (LDs) plays an important role in pathological processes associated with abnormal metabolism. Monitoring the variation LDs cells and tissues is great importance biomedical research clinical diagnosis. However, developing fluorescent LDs‐specific probes high sensitivity, brightness, permeability for deep tissue imaging still challenging. Herein, a push–pull luminogen (DPBT) aggregation‐induced emission, strong solvatochromism, large Stokes shift, solid‐state fluorescence efficiency superior two‐photon absorption facilely developed. lipophilic DPBT can specifically stain biocompatibility good photostability. viscosity‐enhanced solvatochromic emission property enables to visualize brightness contrast, penetration depth under microscopy. lipids various mouse (atherosclerotic plaque, liver, mesenteric adipose tissues) map their distribution reflect metabolic states within those tissues. It found that deposition as well hyperlipoidemia are clearly different from normal mouse. Its excellent properties make promising candidate investigating LDs‐associated physiological live biological samples.

Language: Английский

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