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

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(16), P. 5607 - 5651

Published: Jan. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 145(14), P. 8130 - 8140

Published: March 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.

Language: Английский

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Supramolecular photodynamic agents for simultaneous oxidation of NADH and generation of superoxide radical

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 19, 2022

Abstract Given that Type-I photosensitizers (PSs) have hypoxia tolerance, developing general approaches to prepare PSs is of great importance, but remains a challenge. Here, we report supramolecular strategy for the preparation photodynamic agents, which simultaneously generate strong oxidizing cationic radicals and superoxide radicals, by introducing electron acceptors existing Type-II PSs. As proof-of-concept, three were designed co-assembled with classical PS produce quadruple hydrogen-bonded agents. The photo-induced transfer from adjacent acceptor occurs efficiently, leading generation +• an anionic radical acceptor, further transfers oxygen form O 2 −• . In addition, these agents induce direct photocatalytic oxidation NADH turnover frequency as high 53.7 min −1 , offers oxygen-independent mechanism damage tumors.

Language: Английский

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Efficient NIR-II Type-I AIE Photosensitizer for Mitochondria-Targeted Photodynamic Therapy through Synergistic Apoptosis–Ferroptosis

ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 9110 - 9125

Published: May 5, 2023

Hypoxia, the hallmark of malignant tumors, has been recognized as a major obstacle for photodynamic therapy (PDT). Precisely targeting cancer cells in intricate biological scenarios by hypoxia-resistant photosensitizer (PS) is cornerstone to conquer inevitable tumor recurrence and metastasis. Herein, we describe an organic NIR-II PS (TPEQM-DMA) possessing potent type-I phototherapeutic efficacy overcome intrinsic pitfalls PDT combating hypoxic tumors. TPEQM-DMA exhibited prominent emission (>1000 nm) with aggregation-induced feature efficiently produced superoxide anion hydroxyl radical aggregate state under white light irradiation exclusively through low-O2-dependent photochemical process. The suitable cationic nature assisted accumulate cancerous mitochondria. Meanwhile, impaired cellular redox homeostasis, led mitochondrial dysfunction, raised level lethal peroxidized lipids, which induced apoptosis ferroptosis. This synergistic cell death modality enabled suppress growth cells, multicellular spheroids, To improve pharmacological properties TPEQM-DMA, nanoparticles were prepared encapsulation polymer. In vivo experiments proved appealing fluorescence imaging-guided effect

Language: Английский

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Molecular Engineering of pH-Responsive NIR Oxazine Assemblies for Evoking Tumor Ferroptosis via Triggering Lysosomal Dysfunction

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(6), P. 3736 - 3747

Published: Feb. 2, 2023

Ferroptosis, a newly discovered form of regulated cell death, is emerging as promising approach to tumor therapy. However, the spatiotemporal control cell-intrinsic Fenton chemistry modulate ferroptosis remains challenging. Here, we report an oxazine-based activatable molecular assembly (PTO-Biotin Nps), which capable triggering lysosomal dysfunction-mediated pathway with excellent resolution via near-infrared (NIR) light evoke ferroptosis. In this system, pH-responsive NIR photothermal oxazine molecule was designed and functionalized tumor-targeting hydrophilic biotin-poly(ethylene glycol) (PEG) chain engineer well-defined nanostructured assemblies within single-molecular framework. PTO-Biotin Nps possesses selective tropism lysosome accumulation inside cells, accommodated by its enhanced activity in acidic microenvironment. Upon activation, promoted dysfunction induced cytosolic acidification impaired autophagy. More importantly, photoactivation-mediated found markedly enhance cellular reactions ferroptosis, thereby improving antitumor efficacy mitigating systemic side effects. Overall, our study demonstrates that engineering enables modulation intrinsic mechanism, offering novel strategy for development metal-free inducers

Language: Английский

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An ER‐targeted, Viscosity‐sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(9)

Published: Jan. 10, 2024

The concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend modern medical advancement. Herein, we rationally designed smart molecule ER-ZS for endoplasmic reticulum (ER)-targeted diagnosis treatment in cell animal models by combining hemicyanine dyes ER-targeted functional groups (p-toluenesulfonamide). Owing to its ability target ER a highly specific response viscosity, demonstrated substantial fluorescence turn-on only after binding ER, independent other physiological environments. In addition, ER-ZS, being small molecule, allows nonalcoholic fatty liver disease (NAFLD) via imaging based on high stress. Importantly, is type I photosensitizer, producing O

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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Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 11(21), P. 4600 - 4618

Published: Jan. 1, 2023

Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment.

Language: Английский

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Photodynamic therapy combined with immunotherapy: Recent advances and future research directions

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 495, P. 215350 - 215350

Published: Aug. 19, 2023

Innovative anticancer therapies based on the activation of immune system offer promise in battle against cancers resistant to traditional treatments. Examples such therapeutic approaches include, along with various types immunotherapies, photodynamic therapy (PDT). PDT is a photochemistry-based strategy that results not only from its direct effects cancer cells but also disruption tumor vasculature and host system. However, achieve success manifested eradication primary distant metastases, it necessary design suitable photosensitizers (PSs) desired optical photophysical properties enable efficient generation ROS under microenvironmental (TME) conditions, especially hypoxia. Thus, this review particular attention paid photochemical PSs, notably sufficiently long-lived triplet states mechanisms energy/electron transfer reactions. Photogenerated initiate inflammatory reaction, expression heat-shock proteins, infiltration long-term memory. These unique features give new possibilities combine agents stimulating response as well immunotherapy, PD-1/PD-L1 blockade. Most systems explored aspect so far are either derivatives naturally occurring metal complexes (Heme, Chlorophyll a, Bacteiochorophyll - inspired PSs), synthetic (metallo)porphyrins, (metallo)phthalocyanines or hybrid materials containing nanoparticles. This work summarizes recent reports synthesis antibody-PS conjugates spectroscopic enhanced selectivity biological activity. Finally, most notable drawbacks presented, scenario outlined for development alone, combined immunotherapy overcome these challenges future.

Language: Английский

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