An Activatable Phototheranostic Probe for Anti‐hypoxic Type I Photodynamic‐ and Immuno‐Therapy of Cancer

Advanced Materials, Год журнала: 2023, Номер 36(4)

Опубликована: Авг. 29, 2023

Photodynamic therapy (PDT), which utilizes type I photoreactions, has great potential as an effective cancer treatment because of its hypoxia-tolerant superiority over the commonly used II pathway. A few photosensitizers are exploited; however, they majorly induce cytotoxicity and possess poor tumor specificity low-efficient theranostics. To resolve this issue, herein aminopeptidase N (APN)-activated phototheranostic probe (CyA) is reported for anti-hypoxic PDT in conjunction with immunotherapy treatment. CyA can specifically activate near-infrared fluorescence, photoacoustic signals, phototoxicity following APN-induced substrate cleavage subsequent generation active molecules (such CyBr). endows specific imaging capabilities toward cells overexpressing APN under both normoxia hypoxia. In addition, locally activatable induces systemic antitumor immune responses. More importantly, integration localized activated evokes enhanced therapeutic effects improved inhibition efficiency live mice compared individual treatments. This study aims to present combination therapy.

Язык: Английский

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Photo‐Induced Disproportionation‐Mediated Photodynamic Therapy: Simultaneous Oxidation of Tetrahydrobiopterin and Generation of Superoxide Radicals

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(12)

Опубликована: Янв. 23, 2024

We herein present an approach of photo-induced disproportionation for preparation Type-I photodynamic agents. As a proof concept, BODIPY-based photosensitizers were rationally designed and prepared. The intermolecular electron transfer between homotypic chromophores leads to the reaction, resulting in formation charged intermediates, cationic anionic radicals. radicals efficiently oxidize cellularimportant coenzyme, tetrahydrobiopterin (BH

Язык: Английский

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Supramolecular systems for bioapplications: recent research progress in China

Science China Chemistry, Год журнала: 2024, Номер 67(5), С. 1397 - 1441

Опубликована: Март 22, 2024

Язык: Английский

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Photoactivation Inducing Multifunctional Coupling of Fluorophore for Efficient Tumor Therapy In Situ

Advanced Materials, Год журнала: 2024, Номер 36(23)

Опубликована: Фев. 15, 2024

Abstract Photoactivatable molecules, with high‐precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor ( BI ) is described that can be triggered by broad excitation light (405–660 nm), which further undergoes intersystem crossing H‐atom transfer processes to forming superoxide anion radicals (O 2 −• carbon radicals. Particularly, photoinduced gain carbon‐centered BI• allows for radical‐radical coupling afford combined crosslink product BI─BI ), would oxidized in presence O produce an extended conjugate system near infrared emission (820 nm). Besides, photochemically generated Cy─BI possesses ultra‐high photothermal conversion efficiency up 90.9%, optimized potential. What′s more, Western Blot assay reveals both photoproduct efficiently inhibit expression CHK1, irradiation induces apoptosis ultimately enhances phototherapeutic effects. Thus, combination cell cycle block inducing apoptosis, photodynamic therapy treatments significantly suppress solid tumor vivo antitumor efficacy explorations. This a novel finding developing as well applicability photoimaging tumor‐related areas.

Язык: Английский

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RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(36), С. 25270 - 25281

Опубликована: Авг. 31, 2024

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for treatment of cancer. Existing photosensitizers are predominantly engineered target diverse biomolecules, including proteins, DNA, lipids, carbohydrates, have proven greatly enhance efficacy or specificity PDT. However, it is noteworthy that there exists a conspicuous scarcity specifically designed RNAs. Recognizing crucial multifaceted roles played by RNAs in various cellular processes disease states, we ventured into development novel RNA-targeting photosensitizer, named Se-718, PDT-based cancer therapy. Se-718 been exhibit high molar absorption coefficient NIR region, which effective More importantly, demonstrated distinct capability, evidenced through rigorous testing both circular dichroism fluorescence experiments. Furthermore, shown display type I II photodynamic properties. This unique characteristic enables efficient killing cells under wide range oxygen conditions, normoxic (21% O2) hypoxic (2% O2). The IC50 can be low 100 nM, its light-to-dark toxicity ratio impressive 215 times higher, outperforming most currently available. Moreover, vivo studies conducted with tumor-bearing mice excellent antitumor effects safety profile Se-718. Considering outstanding PDT optimistic may provide innovative highly option therapeutics near future.

Язык: Английский

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Engineered hypoxia-responsive albumin nanoparticles mediating mitophagy regulation for cancer therapy

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 11, 2025

Hypoxic tumors present a significant challenge in cancer therapy due to their ability adaptation low-oxygen environments, which supports tumor survival and resistance treatment. Enhanced mitophagy, the selective degradation of mitochondria by autophagy, is crucial mechanism that helps sustain cellular homeostasis hypoxic tumors. In this study, we develop an azocalix[4]arene-modified supramolecular albumin nanoparticle, co-delivers hydroxychloroquine mitochondria-targeting photosensitizer, designed induce cascaded oxidative stress regulating mitophagy for treatment These nanoparticles are hypoxia-responsive release loaded guest molecules cells. The released disrupts process, thereby increasing further weakening Additionally, upon laser irradiation, photosensitizer generates reactive oxygen species independent oxygen, inducing damage activation. dual action simultaneous spatiotemporal activation flux blockade results enhanced autophagic stress, ultimately driving cell death. Our work highlights effectiveness hydroxychloroquine-mediated combined with mitochondria-targeted cascade-amplified against has been recognized as Here, group fabricates nanoparticle codelivering (HCQ) sulfur-substituted methylated nile blue analog, capable via

Язык: Английский

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Hemicyanine-Based Type I Photosensitizers for Antihypoxic Activatable Photodynamic Therapy

ACS Materials Letters, Год журнала: 2023, Номер 5(11), С. 3058 - 3067

Опубликована: Окт. 20, 2023

Type I photosensitizers provide great potential for effective antihypoxia cancer treatment because of their low O2 reliance. To achieve tumor specificity, activatable type that can selectively respond to tumor-related stimuli and thereafter activate phototoxicity are urgently required, which however rare. We herein report a hemicyanine-based scaffold with photoreactions antihypoxic PDT against tumors. The common hemicyanine (Cy) endows minimized ROS generation, be nicely tuned boost production by introducing the halogens increase spin–orbit coupling (SOC) constant thus favor intersystem crossing (ISC) rate. optimized CyBr is further modified an probe (CyBrP) specifically unlock its fluoro-photoacoustic signals upon interaction alkaline phosphatase (ALP) overexpressed in By virtue high sensitivity selectivity toward ALP as well O2-dependence CyBrP allows precise phototheranostics tumors, leading effectively suppressed growth living mice. Therefore, this study presents facile halogen-substituted strategy construct serve universal scaffolds PDT.

Язык: Английский

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Organic‐Platinum Hybrids for Covalent Binding of G‐Quadruplexes: Structural Basis and Application to Cancer Immunotherapy

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(36)

Опубликована: Июль 19, 2023

G-quadruplexes (G4s) have been revived as promising therapeutic targets with the development of immunotherapy, but G4-mediated immune response remains unclear. We designed a novel class G4-binding organic-platinum hybrids, L1 -cispt and -transpt, spatial matching for G4 binding DNA reactivity site locking. The solution structure -transpt-MYT1L demonstrated effectiveness covalent revealed binding-guided dynamic balance, accompanied by destruction A5-T17 base pairs to achieve platinum unit N7 G6 residue. Furthermore, -cispt- -transpt-mediated genomic dysfunction could activate retinoic acid-induced gene I (RIG-I) pathway induce immunogenic cell death (ICD). use -cispt/L1 -transpt-treated dying cells vaccines stimulated robust effectively inhibited tumor growth in vivo. Our findings highlight importance rational combination specific recognition locking G4-trageting drug design their potential immunotherapy.

Язык: Английский

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Rhenium(I) coordinated carbon nitride as type II immunogenic cell death inducers for enhancing photoimmunotherapy against triple-negative breast cancer

Chemical Engineering Journal, Год журнала: 2024, Номер 485, С. 150154 - 150154

Опубликована: Март 2, 2024

Язык: Английский

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Targeting paraptosis in cancer: opportunities and challenges

Cancer Gene Therapy, Год журнала: 2024, Номер 31(3), С. 349 - 363

Опубликована: Янв. 4, 2024

Язык: Английский

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