Organic Photodynamic Nanoinhibitor for Synergistic Cancer Therapy

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(24), С. 8161 - 8165

Опубликована: Апрель 17, 2019

Despite its great potential in cancer treatment, photodynamic therapy (PDT) often exacerbates hypoxia and subsequently compromises therapeutic efficacy. To overcome this issue, an organic nanoinhibitor (OPNi) has been synthesized that the additional ability to counteract carbonic anhydrase IX (CA-IX), a molecular target hypoxia-mediated signalling cascade. OPNi is composed of metabolizable semiconducting polymer as photosensitizer CA-IX antagonist conjugated amphiphilic matrix. This structure allows not only selectively bind positive cells facilitate tumor accumulation but also regulate CA-IX-related pathway. The integration inhibition into targeted PDT process eventually synergistic effect, leading superior antitumor efficacy over alone, well reduced probability hypoxia-induced metastasis. study thus proposes strategy devise simple yet amplified photosensitizers conquer pitfalls traditional PDT.

Язык: Английский

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A Multi‐action and Multi‐target Ru^II–Pt^IV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(18), С. 7069 - 7075

Опубликована: Фев. 4, 2020

Abstract Pt II complexes are commonly used to treat cancer. To reduce their side effects and improve pharmacological properties, IV being developed as prodrug candidates that activated by reduction in cancer cells. Concomitantly, Ru polypyridine have gained much attention photosensitizers for use photodynamic therapy due attractive characteristics. In this article, a novel –Ru conjugate, which combines chemotherapy with PDT, is presented. Upon entering the cell, centre reduced axial ligands including complex phenylbutyrate released. As each component has its individual targets, conjugate exerts multi‐target multi‐action effect (photo‐)cytotoxicity values upon irradiation up 595 nm low nanomolar range various (drug resistant) 2D monolayer cells 3D multicellular tumour spheroids.

Язык: Английский

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Polymeric Nanoparticles with ROS‐Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer

Advanced Science, Год журнала: 2020, Номер 7(20)

Опубликована: Сен. 6, 2020

Abstract The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment cancer. However, are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, hypoxia‐associated poor PDT efficacy solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)‐responsive prodrug nanoparticle (CPT‐TK‐HPPH/Pt NP) is created to overcome these limitations. ROS‐responsive consists thioketal bond linked with camptothecin (CPT) photosensitizer‐2‐(1‐hexyloxyethyl)‐2‐devinyl pyropheophorbide‐a (HPPH). PtNP CPT‐TK‐HPPH/Pt NP can efficiently catalyze decomposition hydrogen peroxide (H 2 O ) into relieve hypoxia. production satisfy consumption HPPH under 660 nm laser irradiation attain on‐demand CPT ensure enhanced therapy. As tumor diagnosis agent, results photoacoustic imaging fluorescence for exhibit desirable long circulation vivo targeting. NPs effectively inhibit proliferation growth vitro vivo. NP, its excellent drug behavior efficiency serve as new cancer theranostic will further promote research chemophotodynamic

Язык: Английский

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In Situ Hypoxia-Induced Supramolecular Perylene Diimide Radical Anions in Tumors for Photothermal Therapy with Improved Specificity

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(5), С. 2360 - 2367

Опубликована: Янв. 20, 2022

Considering that hypoxia is closely associated with tumor proliferation, invasion, metastasis, and drug resistance, it of great significance to overcome in treatment. Herein, we report a hypoxia-induced specific photothermal therapy (PTT) based on the agent supramolecular perylene diimide radical anions. Hypoxic regions various tumors display strong reductive ability, such environments complex derivative cucurbit[7]uril could be reduced Benefiting from NIR absorption good conversion performance situ generated anions, PTT strategy exhibits excellent therapeutic efficiency as well specificity biological safety. Moreover, inducible factor expression decreases normal level after It anticipated opens new horizons for against hypoxic improved

Язык: Английский

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Nanostructured Phthalocyanine Assemblies with Efficient Synergistic Effect of Type I Photoreaction and Photothermal Action to Overcome Tumor Hypoxia in Photodynamic Therapy

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(34), С. 13980 - 13989

Опубликована: Авг. 24, 2021

Most photodynamic therapy (PDT) paradigms work through the highly O2-dependent type II photoreaction to generate singlet oxygen (1O2). The hypoxic microenvironment of solid tumors severely hampers therapeutic outcomes. Here, we present a novel design that could transfer photophysical and photochemical properties traditional phthalocyanine-based photosensitizers from efficient I vibrational relaxation-induced photothermal conversion. These features enable obtained nanostructured phthalocyanine assemblies (e.g., NanoPcAF) display excellent phototherapies under both normoxic conditions. Moreover, NanoPcAF has high level accumulation in tumor tissues after intravenous injection, 94% growth is inhibited preclinical model at dose 0.8 nmol g–1 light 300 J cm–2.

Язык: Английский

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Photodecaging of a Mitochondria-Localized Iridium(III) Endoperoxide Complex for Two-Photon Photoactivated Therapy under Hypoxia

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(9), С. 4091 - 4101

Опубликована: Фев. 16, 2022

Despite the clinical success of photodynamic therapy (PDT), application this medical technique is intrinsically limited by low oxygen concentrations found in cancer tumors, hampering production therapeutically necessary singlet (1O2). To overcome limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (2-O-IrAn), which, upon two-photon irradiation NIR, synergistically releases highly cytotoxic complex (2-IrAn), oxygen, and an alkoxy radical. 2-O-IrAn was to be (photo-)toxic hypoxic tumor cells multicellular spheroids (MCTS) nanomolar range. provide selectivity improve pharmacological properties 2-O-IrAn, it encapsulated into biotin-functionalized polymer. The generated nanoparticles were nearly fully eradicate inside mouse model within single treatment. This study presents, best our knowledge, first example iridium(III)-based for synergistic therapy/photoactivated chemotherapy, opening up new avenues treatment tumors.

Язык: Английский

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Harnessing Endogenous Stimuli for Responsive Materials in Theranostics

ACS Nano, Год журнала: 2021, Номер 15(2), С. 2068 - 2098

Опубликована: Фев. 8, 2021

Materials that respond to endogenous stimuli are being leveraged enhance spatiotemporal control in a range of biomedical applications from drug delivery diagnostic tools. The design materials undergo morphological or chemical changes response specific biological cues pathologies will be an important area research for improving efficacies existing therapies and imaging agents, while also promising developing personalized theranostic systems. Internal stimuli-responsive systems can engineered across length scales nanometers macroscopic signals such as enzymes, pH, glucose, ATP, hypoxia, redox signals, nucleic acids by incorporating synthetic bio-inspired moieties natural building blocks. This Review summarize mechanisms fabrication strategies used internal with focus on broad pathologies, including cancer, diabetes, vascular disorders, inflammation, microbial infections. We discuss observed challenges, future directions, clinical translation aspects these responsive materials.

Язык: Английский

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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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A Biodegradable Iridium(III) Coordination Polymer for Enhanced Two‐Photon Photodynamic Therapy Using an Apoptosis–Ferroptosis Hybrid Pathway

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(28)

Опубликована: Май 9, 2022

Abstract The clinical application of photodynamic therapy is hindered by the high glutathione concentration, poor cancer‐targeting properties, drug loading into delivery systems, and an inefficient activation cell death machinery in cancer cells. To overcome these limitations, herein, formulation a promising Ir III complex biodegradable coordination polymer ( IrS NPs ) presented. nanoparticles were found to remain stable under physiological conditions but deplete disintegrate monomeric metal complexes tumor microenvironment, causing enhanced therapeutic effect. selectively accumulate mitochondria where trigger hybrid apoptosis ferroptosis pathways through photoinduced production singlet oxygen superoxide anion radicals. This study presents first example that can efficiently cause upon irradiation, providing innovative approach for therapy.

Язык: Английский

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

ACS Nano, Год журнала: 2023, Номер 17(10), С. 9110 - 9125

Опубликована: Май 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

Язык: Английский

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