Supramolecular Photosensitizer Enables Oxygen-Independent Generation of Hydroxyl Radicals for Photodynamic Therapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 4081 - 4087

Published: Feb. 13, 2023

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop oxygen-independent supramolecular agent that produces hydroxyl radical (•OH) by oxidizing water the presence intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as electron donor and coassembled with perylene diimide acceptor form quadruple hydrogen-bonded agent. Detailed mechanism studies reveal intermolecular transfer charge separation upon light irradiation result efficient generation ion pairs. Under conditions, cationic radicals directly oxidize generate cytotoxic •OH, anionic electrons acid, realizing catalytic cycle. Thus, this exhibited superb photocytotoxicity even severe environments excellent vivo antitumor on HeLa-bearing mouse models. This work provides a strategy for constructing agents, opens up avenue effective PDT tumors.

Language: Английский

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Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6007 - 6023

Published: March 7, 2023

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by release pro-inflammatory cytokines. Our knowledge pyroptosis has expanded beyond cellular level and now includes extracellular responses. In recent years, attracted considerable attention due its potential induce host immunity. For instance, at 2022 International Medicinal Chemistry Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled activation ("PhotoPyro"), emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share Perspective our views on area expound how why "PhotoPyro" could trigger antitumor (i.e., turning so-called "cold" tumors "hot"). doing so, have tried highlight cutting-edge breakthroughs PhotoPyro while suggesting areas future contributions. By providing insights into current state art serving as a resource individuals interested working area, it is hoped that will set stage evolve broadly applicable cancer treatment strategy.

Language: Английский

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Nanoparticle‐Based Photothermal Therapy for Breast Cancer Noninvasive Treatment

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 10, 2023

Rapid advancements in materials science and nanotechnology, intertwined with oncology, have positioned photothermal therapy (PTT) as a promising noninvasive treatment strategy for cancer. The breast's superficial anatomical location aesthetic significance render breast cancer particularly pertinent candidate the clinical application of PTT following melanoma. This review comprehensively explores research conducted on various types nanoparticles employed elaborates their specific roles mechanisms action. integration existing therapies is scrutinized, underscoring its potential synergistic outcomes. Additionally, underlying consequential modifications to tumor microenvironment after are elaborated from medical perspective. Future directions suggested, an emphasis development integrative platforms that combine multiple therapeutic approaches optimization nanoparticle synthesis enhanced efficacy. goal push boundaries toward comprehensive, clinically applicable

Language: Английский

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Enzyme-Responsive Double-Locked Photodynamic Molecular Beacon for Targeted Photodynamic Anticancer Therapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(13), P. 7361 - 7375

Published: March 24, 2023

An advanced photodynamic molecular beacon (PMB) was designed and synthesized, in which a distyryl boron dipyrromethene (DSBDP)-based photosensitizer Black Hole Quencher 3 moiety were connected via two peptide segments containing the sequences PLGVR GFLG, respectively, of cyclic peptide. These short are well-known substrates matrix metalloproteinase-2 (MMP-2) cathepsin B, both overexpressed wide range cancer cells either extracellularly (for MMP-2) or intracellularly B). Owing to efficient Förster resonance energy transfer between components, this PMB fully quenched native form. Only upon interaction with MMP-2 buffer solution cells, cleaved specifically, components could be completely separated, thereby restoring activities DSBDP moiety. This also activated tumors, it effectively suppressed tumor growth A549 tumor-bearing nude mice laser irradiation without causing notable side effects. In particular, did not cause skin photosensitivity, is very common effect therapy (PDT) using conventional "always-on" photosensitizers. The overall results showed that "double-locked" functioned as biological AND logic gate only unlocked by coexistence tumor-associated enzymes, greatly enhance specificity PDT.

Language: Английский

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Activatable nano-photosensitizers for precise photodynamic cancer therapy

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 493, P. 215324 - 215324

Published: July 10, 2023

Language: Английский

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Oxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 21, 2024

Abstract Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design precise side-chain engineering generate •O 2 − •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed skeletons can electron-hole pairs sensitize H O into with photoexcitation, achieving NIR-photoexcited oxygen-independent production. Further, compared commonly used alkyl side chains, glycol oligomer as the chain mitigates recombination offers more molecules around generated from hydrophobic skeletons, which yield 4-fold stronger production, thus allowing an high PDT effect. Finally, feasibility of developing activatable PSs in female mice further demonstrated irradiation 15 mW cm −2 . study not only provides insights mechanism also general guideline develop NIR PDT.

Language: Английский

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

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(4)

Published: Aug. 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.

Language: Английский

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Molecularly Engineered Room-Temperature Phosphorescence for Biomedical Application: From the Visible toward Second Near-Infrared Window

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(24), P. 13966 - 14037

Published: Nov. 22, 2023

Phosphorescence, characterized by luminescent lifetimes significantly longer than that of biological autofluorescence under ambient environment, is great value for biomedical applications. Academic evidence fluorescence imaging indicates virtually all metrics (sensitivity, resolution, and penetration depths) are improved when progressing into wavelength regions, especially the recently reported second near-infrared (NIR-II, 1000–1700 nm) window. Although emission probes does matter, it not clear whether guideline "the wavelength, better effect" still suitable developing phosphorescent probes. For tissue-specific bioimaging, long-lived probes, even if they emit visible phosphorescence, enable accurate visualization large deep tissues. studies dealing with bioimaging tiny architectures or dynamic physiopathological activities, prerequisite rigorous planning long-wavelength being aware cooperative contribution long wavelengths improving spatiotemporal depth, sensitivity bioimaging. In this Review, emerging molecular engineering methods room-temperature phosphorescence discussed through lens photophysical mechanisms. We highlight roles from to NIR-II windows toward bioapplications. To appreciate such advances, challenges prospects in rapidly growing described.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(12)

Published: Jan. 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

Language: Английский

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Mitochondria-Targeting Type-I Photodrug: Harnessing Caspase-3 Activity for Pyroptotic Oncotherapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9413 - 9421

Published: March 20, 2024

Precise control of cellular signaling events during programmed cell death is crucial yet challenging for cancer therapy. The modulation signal transduction in cells holds promise but limited by the lack efficient, biocompatible, and spatiotemporally controllable approaches. Here we report a photodynamic strategy that modulates both apoptotic pyroptotic altering caspase-3 protein activity associated crosstalk. This employs mitochondria-targeting, near-infrared activatable probe (termed M-TOP) functions via type-I photochemical mechanism. M-TOP less dependent on oxygen more effective treating drug-resistant cells, even under hypoxic conditions. Our study shows higher doses induce caspase-3/gasdermin-E pathway, whereas lower lead to apoptosis. method across diverse gasdermin-E-expressing cells. Moreover, mediated shift from can evoke controlled inflammatory response, leading robust balanced immune reaction. effectively inhibits distal tumor growth postsurgical recurrence. work demonstrates feasibility modulating intracellular through rational design anticancer drugs.

Language: Английский

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