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

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 4081 - 4087

Опубликована: Фев. 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.

Язык: Английский

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Fluorescent dyes based on rhodamine derivatives for bioimaging and therapeutics: recent progress, challenges, and prospects

Chemical Society Reviews, Год журнала: 2023, Номер 52(16), С. 5607 - 5651

Опубликована: Янв. 1, 2023

Since their inception, rhodamine dyes have been extensively applied in biotechnology as fluorescent markers or for the detection of biomolecules owing to good optical physical properties. Accordingly, they emerged a powerful tool visualization living systems. In addition fluorescence bioimaging, molecular design derivatives with disease therapeutic functions (e.g., cancer and bacterial infection) has recently attracted increased research attention, which is significantly important construction libraries diagnostic integration. However, reviews focusing on integrated strategies dye-based diagnosis treatment wide application are extremely rare. this review, first, brief history development dyes, transformation from bioimaging therapy, concept optics-based integration its significance human presented. Next, systematic review several excellent rhodamine-based well treatment, Finally, challenges practical future outlook clinical translation also discussed.

Язык: Английский

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Integration of TADF Photosensitizer as “Electron Pump” and BSA as “Electron Reservoir” for Boosting Type I Photodynamic Therapy

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 8130 - 8140

Опубликована: Март 31, 2023

Type I photosensitization provides an effective solution to the problem of unsatisfactory photodynamic therapeutic (PDT) effects caused by tumor hypoxia. The challenge in development mode is boost photosensitizer's own electron transfer capacity. Herein, we found that use bovine serum albumin (BSA) encapsulate a thermally activated delayed fluorescence (TADF) photosensitizer PS can significantly promote PDT process generate mass superoxide anions (O2•–). This opened new strategy employing BSA as "electron reservoir" and TADF pump". We integrated these roles one system preparing nanophotosensitizer PS@BSA. performance was demonstrated with cells under hypoxic conditions. Furthermore, PS@BSA took full advantage tumor-targeting role achieved efficient for tumor-bearing mice vivo experiments. work route improve efficiency tumors.

Язык: Английский

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From Low to No O₂-Dependent Hypoxia Photodynamic Therapy (hPDT): A New Perspective

Accounts of Chemical Research, Год журнала: 2022, Номер 55(22), С. 3253 - 3264

Опубликована: Ноя. 2, 2022

ConspectusThe advent of photochemical techniques has revolutionized the landscape biology and medical sciences. Especially appealing in this context is photodynamic therapy (PDT), which a photon-initiated treatment modality that uses cytotoxic reactive oxygen species (ROS) to kill malignant cells. In past decade, PDT risen forefront cancer therapy. Its optical control enables noninvasive spatiotemporal manipulation process, its photoactive nature allows unique patterns avoid drug resistance conventional chemotherapeutics. However, despite impressive advances field, achieving widespread clinical adoption remains difficult. A major concern hostile tumor microenvironment, cells are hypoxic, hinders ROS generation during action. To overcome "Achilles' heel", current strategies focus primarily on improvement intratumoral O2 perfusion, while trials suggest enrichment may promote cell proliferation metastasis, thereby making FDA approval transformation these paradigms challenging.In an effort improve hypoxia (hPDT) clinic, we have explored "low no O2-dependent" approaches over years combat hypoxia-induced resistance. Account, present our contributions theme 5 years, beginning with low O2-dependent (e.g., type I superoxide radical (O2•–) generator, O2-economizer, mitochondrial respiration inhibition, cellular self-protective pathway modulation, etc.) progressing O2-independent autoadaptive PDT/PTT complementary therapy, artificial photoredox catalysis cells). These studies attracted tremendous attention. Particularly pioneering work 2018, presented first demonstration O2•–-mediated partial O2-recyclability mechanism can ( J. Am. Chem. Soc. 140, 14851−14859). This launched era renewed interest PDT, resulting plethora new O2•– photogenerators developed by many groups around world. Moreover, discovery reactions living cells, emerged as field connecting photochemistry biomedicine, stimulating development next-generation phototherapeutic tools 2022, 144, 163−173). Our recent also disclosed "photoredox cells" might be general action Proc. Natl. Acad. Sci. U.S.A. 119, e2210504119). emergent concepts, molecular designs, mechanisms, applications diagnosis therapeutics, well pros cons, discussed depth Account. It expected date will use researchers inspire future efforts identify more promising hPDT better meet needs

Язык: Английский

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Engineering of BODIPY-based theranostics for cancer therapy

Coordination Chemistry Reviews, Год журнала: 2022, Номер 476, С. 214908 - 214908

Опубликована: Ноя. 7, 2022

Язык: Английский

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Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Год журнала: 2023, Номер 36(8)

Опубликована: Окт. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(11), С. 6007 - 6023

Опубликована: Март 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.

Язык: Английский

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Metal-Based Photosensitizers as Inducers of Regulated Cell Death Mechanisms

Chemical Reviews, Год журнала: 2023, Номер 123(16), С. 10135 - 10155

Опубликована: Авг. 3, 2023

Over the last few decades, various forms of regulated cell death (RCD) have been discovered and were found to improve cancer treatment. Although there are several reviews on RCD induced by photodynamic therapy (PDT), a comprehensive summary covering metal-based photosensitizers (PSs) as inducers has not yet presented. In this review, we systematically summarize works PSs that induce different types RCD, including ferroptosis, immunogenic (ICD), pyroptosis. The characteristics mechanisms each explained. At end section, reported commonalities between inducing same is emphasized, future perspectives novel discussed at review. Considering essential roles in therapy, hope review will provide stage for advances inducers.

Язык: Английский

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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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A Cascade Strategy Boosting Hydroxyl Radical Generation with Aggregation-Induced Emission Photosensitizers-Albumin Complex for Photodynamic Therapy

ACS Nano, Год журнала: 2023, Номер 17(17), С. 16993 - 17003

Опубликована: Авг. 22, 2023

Effective photodynamic therapy (PDT) requires photosensitizers (PSs) to massively generate type I reactive oxygen species (ROS) in a less oxygen-dependent manner the hypoxia tumor microenvironment. Herein, we present cascade strategy boost ROS, especially hydroxyl radical (OH·-), generation with an aggregation-induced emission (AIE) photosensitizer-albumin complex for hypoxia-tolerant PDT. The cationic AIE PS TPAQ-Py-PF6 (TPA = triphenylamine, Q anthraquinone, Py pyridine) contains three important moieties cooperatively enhance free generation: AIE-active TPA unit ensures effective triplet exciton aggregate, anthraquinone moiety possesses redox cycling ability promote electron transfer, while methylpyridinium cation further increases intramolecular charge transfer and separation processes. Inserting into hydrophobic domain of bovine serum albumin nanoparticles (BSA NPs) could greatly immobilize its molecular geometry increase generation, electron-rich microenvironment BSA ultimately leads OH·- generation. Both experimental theoretical results confirm effectiveness our cationization immobilization enhancing In vitro vivo experiments validate excellent antitumor PDT performance NPs, superior conventional polymeric encapsulation approach. Such multidimensional specially boosting shall hold great potential related applications.

Язык: Английский

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