Theranostic Fluorescent Probes

Chemical Reviews, Год журнала: 2024, Номер 124(5), С. 2699 - 2804

Опубликована: Фев. 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.

Язык: Английский

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Engineering high-performance dicyanomethylene-4H-pyran fluorophores for biosensing and phototherapy

Coordination Chemistry Reviews, Год журнала: 2024, Номер 503, С. 215652 - 215652

Опубликована: Янв. 9, 2024

Язык: Английский

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Senolysis Enabled by Senescent Cell‐Sensitive Bioorthogonal Tetrazine Ligation

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(9)

Опубликована: Янв. 18, 2024

Although the clearance of senescent cells has been proven to slow down aging process and promote anti-cancer chemotherapy, development senolytics remains challenging. Herein, we report a senolytic strategy enabled by cell-sensitive bioorthogonal tetrazine ligation. Our design is based on linking dihydrotetrazine (Tz) galactose (Gal) moiety that serves both as recognition for senescence-associated β-galactosidase caging group control activity. Gal-Tz enables efficient click-release fluorescent hemicyanine doxorubicin from trans-cyclooctene-caged prodrug detect eliminate HeLa A549 over non-senescent counterparts with 16.44 index. Furthermore, leverage selective activation delivery proteolysis-targeting chimeras (PROTACs) senolytics. PROTAC TCO-ARV-771 can be selectively activated delivered into induce degradation bromodomain-containing protein 4. Senolytic PROTACs may offer an way intervention cell senescence thanks their unique capacity degrade target proteins in sub-stoichiometric catalytic fashion. The results this study establish ligation approach viable removal cells.

Язык: Английский

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Selective Elimination of Senescent Cancer Cells by Galacto-Modified PROTACs

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(9), С. 7301 - 7311

Опубликована: Апрель 18, 2024

Although the selective and effective clearance of senescent cancer cells can improve treatment, their development is confronted by many challenges. As part efforts designed to overcome these problems, prodrugs, whose design based on senescence-associated β-galactosidase (SA-β-gal), have been developed selectively eliminate cells. However, chemotherapies relying targeted molecular inhibitors as senolytic drugs induce drug resistance. In current investigation, we devised a new strategy for degradation target proteins in that utilizes prodrug composed SA-β-gal substrate galactose (galacto) proteolysis-targeting chimeras (PROTACs) agents. Prodrugs Gal-ARV-771 Gal-MS99 were found display indexes higher than those ARV-771 MS99. Significantly, results vivo studies utilizing human lung A549 xenograft mouse model demonstrated concomitant treatment with etoposide leads significant inhibition tumor growth without eliciting toxicity.

Язык: Английский

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Activatable Fluorescent Probe for Studying Drug-Induced Senescence In Vitro and In Vivo

Analytical Chemistry, Год журнала: 2024, Номер 96(29), С. 12189 - 12196

Опубликована: Июль 8, 2024

Aging represents a significant risk factor for compromised tissue function and the development of chronic diseases in human body. This process is intricately linked to oxidative stress, with HClO serving as vital reactive oxygen species (ROS) within biological systems due its strong properties. Hence, conducting thorough examination context aging crucial advancing field biology. In this work, we successfully developed fluorescent probe, OPD, tailored specifically detecting senescent cells vivo. Impressively, OPD exhibited robust reaction HClO, showcasing outstanding selectivity, sensitivity, photostability. Notably, effectively identified first time, confirming that DOX- ROS-induced higher levels compared uninduced normal cells. Additionally, vivo imaging zebrafish demonstrated d-galactose- ROS-stimulated displayed elevated zebrafish. Furthermore, when applied mouse tissues organs, revealed increased fluorescence organs mice their nonsenescent counterparts. Our findings also illustrated probe's potential changes content pre- post-aging living mice. Overall, probe holds immense promise valuable tool detection studying biology live organisms.

Язык: Английский

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Activatable Near‐Infrared Versatile Fluorescent and Chemiluminescent Dyes Based on the Dicyanomethylene‐4H‐pyran Scaffold: From Design to Imaging and Theranostics

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(6)

Опубликована: Окт. 19, 2023

Abstract Activatable fluorescent and chemiluminescent dyes with near‐infrared emission have indispensable roles in the fields of bioimaging, molecular prodrugs, phototheranostic agents. As one most popular fluorophore scaffolds, dicyanomethylene‐4 H ‐pyran scaffold has been applied to fabricate a large number versatile activatable optical for analytes detection diseases diagnosis treatment by virtue its high photostability, Stokes shift, considerable two‐photon absorption cross‐section, structural modifiability. This review discusses design strategies, recognition mechanisms, both vitro vivo bio‐applications (especially therapy tumors) dyes. The final section describes current shortcomings future development prospects this topic.

Язык: Английский

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3D Cryo‐Printed Hierarchical Porous Scaffolds Harmonized with Hybrid Nanozymes for Combinatorial Mitochondrial Therapy: Enhanced Diabetic Bone Regeneration via Micromilieu Remodeling

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Апрель 13, 2024

Abstract Regeneration of bone defects in diabetic patients has always been a significant challenge clinical treatment. The pathologic micromilieu, characterized by mitochondrial dysfunction, excessive reactive oxygen species (ROS) accumulation, cellular senescence, and chronic inflammation, compromises innate healing capacity. 3D cryo‐printing technology is utilized tissue engineering to fabricate hierarchical porous scaffolds that promote conducive microenvironment for adhesion, migration, proliferation, nutrient exchange. Nanozymes are used as synthetic mimics natural enzymes scavenge ROS, addressing the limitations antioxidative enzymes. To remodel regeneration cryo‐printed polyaryletherketone with carboxyl groups (PAEK‐COOH) 45S5 bioactive glass (BG) scaffold (PBG scaffold), harmonized hybrid nanozymes comprising SS31‐enhanced manganese dioxide (MnO 2 )‐ferritin biomimetic nanozyme (MF@S nanozyme), developed combinatorial therapy. MF@S specifically targets mitochondria enhance function, ROS accumulated mitochondria, suppress (mtROS) production, thus rejuvenate aging cells, regulate macrophage polarization, modulate differentiation osteoblasts osteoclasts. This PBG‐MF@S combines therapy system micromilieu presents promising therapeutic approach diabetes.

Язык: Английский

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Senolytic Therapy Enabled by Senescent Cell‐Sensitive Biomimetic Melanin Nano‐senolytics

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Май 26, 2024

Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses challenge achieving optimal outcomes. Despite recent occurrence nanomaterial-based approaches targeting SnCs, limited therapeutic effects, potential toxicity still remain major concern. Herein, "double locks-like" nanoplatform developed that integrated Galactan coating mesoporous polydopamine to encase senolytic drug DQ. By this way, DQ only released SnCs are featured with higher levels β-galactosidase (β-gal) low PH. Additionally, nanoparticles equipped 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) gain enhanced photothermal converting potential. Consequently, synthesized nanosenolytics demonstrate remarkable specificity efficacy eradicating accordingly reverse pulmonary fibrosis mice without affecting normal tissues. Upon exposure near-infrared (NIR) light, efficiently remove tumor inducted by chemotherapy, thereby hindering outgrowth metastasis or breast cancer. Collectively, present study develops an "On/Off" switchable response produces more safe, efficient, feasible way delay alleviate age-associated diseases.

Язык: Английский

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Self-adaptive photodynamic therapy for boosting therapeutic efficiency in tumor

Science China Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies

Journal of Translational Internal Medicine, Год журнала: 2025, Номер 13(1), С. 33 - 47

Опубликована: Фев. 1, 2025

Aging and age-related diseases are major drivers of multimorbidity mortality worldwide. Cellular senescence is a hallmark aging. The accumulation senescent cells causally associated with pathogenesis various age-associated disorders. Due to their promise for alleviating disorders extending healthspan, therapeutic strategies targeting (senotherapies) as means combat aging have received much attention over the past decade. Among conventionally used approaches, one usage small-molecule compounds specifically exhibit cytotoxicity toward or inhibit deleterious effects senescence-associated secretory phenotype (SASP). Alternatively, there immunotherapies directed at surface antigens upregulated in (seno-antigens), including chimeric antigen receptor (CAR) therapies senolytic vaccines. This review gives an update current status discovery development therapies, translational progress from preclinical clinical trials. We highlight challenges faced by senotherapeutic context heterogeneity, aim offering novel perspectives future anti-aging interventions aimed enhancing healthy longevity.

Язык: Английский

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