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1.
Proc Natl Acad Sci U S A ; 121(9): e2314620121, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38381784

RESUMO

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal that the photocatalyst lutetium texaphyrin (MLu) facilitates rapid and direct photoredox oxidation of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and various amino acids, thereby triggering pyroptosis through the caspase 3/GSDME pathway. This mechanism is distinct from the well-established role of MLu as a photodynamic therapy sensitizer in cells. Two analogs of MLu, bearing different coordinated central metal cations, were also explored as controls. The first control, gadolinium texaphyrin (MGd), is a weak photocatalyst but generates reactive oxygen species (ROS) efficiently. The second control, manganese texaphyrin (MMn), is ineffective as both a photocatalyst and a ROS generator. Neither MGd nor MMn was found to trigger pyroptosis under the conditions where MLu was active. Even in the presence of a ROS scavenger, treating MDA-MB-231 cells with MLu at concentrations as low as 50 nM still allows for pyroptosis photo-activation. The present findings highlight how biomolecular photoredox catalysis could contribute to pyroptosis activation by mechanisms largely independent of ROS.


Assuntos
Metaloporfirinas , Piroptose , Espécies Reativas de Oxigênio/metabolismo
2.
J Am Chem Soc ; 146(7): 4620-4631, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38330912

RESUMO

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Técnicas Fotoacústicas , Animais , Camundongos , Pirróis/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Nanopartículas/química , Tomografia Computadorizada por Raios X , Técnicas Fotoacústicas/métodos , Linhagem Celular Tumoral , Fototerapia
3.
J Am Chem Soc ; 145(40): 22206-22212, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37751361

RESUMO

Deferasirox is an FDA-approved iron chelator used in the treatment of iron toxicity. In this work, we report the use of several deferasirox derivatives as lanthanide chelators. Solid-state structural studies of three representative trivalent lanthanide cations, La(III), Eu(III), and Lu(III), revealed the formation of 2:2 complexes in the solid state. A 1:1 stoichiometry dominates in DMSO solution, with Ka values of 472 ± 14, 477 ± 11, and 496 ± 15 M-1 being obtained in the case of these three cations, respectively. Under the conditions of competitive precipitation in the presence of triethylamine, high selectivity (up to 80%) for lutetium(III) was observed in competition with La(III), Ce(III), and Eu(III). Theoretical calculations provided support for the observed selective crystallization.

4.
Ultrason Sonochem ; 99: 106559, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37643498

RESUMO

Sonochemistry is the use of ultrasound to generate highly reactive radical species through the inertial collapse of a gas/vapour cavity and is a green alternative for hydrogen production, wastewater treatment, and chemical synthesis and modifications. Yet, current sonochemical reactors often are limited by their design, resulting in low efficacy and yields with slow reaction kinetics. Here, we constructed a novel sonochemical reactor design that creates cylindrically converging ultrasound waves to create an intense localised region of high acoustic pressure amplitudes (15 MPaPKPK) capable of spontaneously nucleating cavitation. Using a novel dosimetry technique, we determined the effect of acoustic parameters on the yield of hydroxyl radicals (HO), HO production rate, and ultimately the sonochemical efficiency (SE) of our reactor. Our reactor design had a significantly higher HO production rate and SE compared to other conventional reactors and across literature.

5.
J Am Chem Soc ; 145(24): 12998-13002, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37283248

RESUMO

Platinum(IV) anticancer agents have demonstrated the potential to overcome the limitations associated with the widely used Pt(II) chemotherapeutics, cisplatin, carboplatin, and oxaliplatin. In order to identify therapeutic scenarios where this type of chemotherapy can be applied, an improved understanding on the intracellular reduction of Pt(IV) complexes is needed. Here, we report the synthesis of two fluorescence responsive oxaliplatin(IV)(OxPt) complexes, OxaliRes and OxaliNap. Sodium ascorbate (NaAsc) was shown to reduce each OxPt(IV) complex resulting in increases in their respective fluorescence emission intensities at 585 and 545 nm. The incubation of each OxPt(IV) complex with a colorectal cancer cell line resulted in minimal changes to the respective fluorescence emission intensities. In contrast, the treatment of these cells with NaAsc showed a dose-dependent increase in fluorescence emission intensity. With this knowledge in hand, we tested the reducing potential of tumor hypoxia, where an oxygen-dependent bioreduction was observed for each OxPt(IV) complex with <0.1% O2 providing the greatest fluorescence signal. Clonogenic cell survival assays correlated with these observations demonstrating significant differences in toxicity between hypoxia (<0.1% O2) and normoxia (21% O2). To the best of our knowledge, this is the first report showing carbamate-functionalized OxPt(IV) complexes as potential hypoxia-activated prodrugs.


Assuntos
Antineoplásicos , Neoplasias , Oxalidaceae , Pró-Fármacos , Oxaliplatina/farmacologia , Fluorescência , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Cisplatino , Platina , Pró-Fármacos/farmacologia
6.
Chem Commun (Camb) ; 59(53): 8278-8281, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37318211

RESUMO

A nitroreductase (NTR) responsive fluorescent probe with long wavelength fluorescence emission was used to determine the NTR activity of a selection of bacterial species under a range of different bacterial growth conditions ensuring applicability under multiple complex clinical environments, where sensitivity, reaction time, and the detection accuracy were suitable for planktonic cultures and biofilms.


Assuntos
Corantes Fluorescentes , Nitrorredutases , Microscopia de Fluorescência
7.
Chem Commun (Camb) ; 59(29): 4328-4331, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36942986

RESUMO

We report the synthesis of hydroxyl-radical (˙OH) responsive fluorescent probes that utilise the 3,5-dihydroxybenzyl (DHB) functionality. 4-Methylumbeliferone-DHB (Umb-DHB) and resorufin-DHB (Res-DHB) in the presence of ˙OH radicals resulted in significant increases in their respective fluorescent emission intensities at 460 nm and 585 nm. The incubation of Res-DHB in HeLa cells followed by therapeutic ultrasound (1 MHz) resulted in a significant increase in fluorescence emission intensity thus permitting the ability to monitor ultrasound-induced ˙OH production in live cells.


Assuntos
Hidroxibenzoatos , Radical Hidroxila , Humanos , Fluorescência , Corantes Fluorescentes , Células HeLa
8.
Chem Soc Rev ; 52(3): 879-920, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36637396

RESUMO

Cancer remains as one of the most significant health problems, with approximately 19 million people diagnosed worldwide each year. Chemotherapy is a routinely used method to treat cancer patients. However, current treatment options lack the appropriate selectivity for cancer cells, are prone to resistance mechanisms, and are plagued with dose-limiting toxicities. As such, researchers have devoted their attention to developing prodrug-based strategies that have the potential to overcome these limitations. This tutorial review highlights recently developed prodrug strategies for cancer therapy. Prodrug examples that provide an integrated diagnostic (fluorescent, photoacoustic, and magnetic resonance imaging) response, which are referred to as theranostics, are also discussed. Owing to the non-invasive nature of light (and X-rays), we have discussed external excitation prodrug strategies as well as examples of activatable photosensitizers that enhance the precision of photodynamic therapy/photothermal therapy. Activatable photosensitizers/photothermal agents can be seen as analogous to prodrugs, with their phototherapeutic properties at a specific wavelength activated in the presence of disease-related biomarkers. We discuss each design strategy and illustrate the importance of targeting biomarkers specific to the tumour microenvironment and biomarkers that are known to be overexpressed within cancer cells. Moreover, we discuss the advantages of each approach and highlight their inherent limitations. We hope in doing so, the reader will appreciate the current challenges and available opportunities in the field and inspire subsequent generations to pursue this crucial area of cancer research.


Assuntos
Neoplasias , Fotoquimioterapia , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
9.
Chem Soc Rev ; 52(2): 601-662, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36149439

RESUMO

Chemical warfare agents (CWAs) are toxic chemicals that have been intentionally developed for targeted and deadly use on humans. Although intended for military targets, the use of CWAs more often than not results in mass civilian casualties. To prevent further atrocities from occurring during conflicts, a global ban was implemented through the chemical weapons convention, with the aim of eliminating the development, stockpiling, and use of CWAs. Unfortunately, because of their relatively low cost, ease of manufacture and effectiveness on mass populations, CWAs still exist in today's world. CWAs have been used in several recent terrorist-related incidents and conflicts (e.g., Syria). Therefore, they continue to remain serious threats to public health and safety and to global peace and stability. Analytical methods that can accurately detect CWAs are essential to global security measures and for forensic analysis. Small molecule fluorescent probes have emerged as attractive chemical tools for CWA detection, due to their simplicity, ease of use, excellent selectivity and high sensitivity, as well as their ability to be translated into handheld devices. This includes the ability to non-invasively image CWA distribution within living systems (in vitro and in vivo) to permit in-depth evaluation of their biological interactions and allow potential identification of therapeutic countermeasures. In this review, we provide an overview of the various reported fluorescent probes that have been designed for the detection of CWAs. The mechanism for CWA detection, change in optical output and application for each fluorescent probe are described in detail. The limitations and challenges of currently developed fluorescent probes are discussed providing insight into the future development of this research area. We hope the information provided in this review will give readers a clear understanding of how to design a fluorescent probe for the detection of a specific CWA. We anticipate that this will advance our security systems and provide new tools for environmental and toxicology monitoring.


Assuntos
Substâncias para a Guerra Química , Humanos , Substâncias para a Guerra Química/análise , Corantes Fluorescentes
10.
Sci Bull (Beijing) ; 67(8): 853-878, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-36546238

RESUMO

Fluorescent probes have emerged as indispensable chemical tools to the field of chemical biology and medicine. The ability to detect intracellular species and monitor physiological processes has not only advanced our knowledge in biology but has provided new approaches towards disease diagnosis. In this review, we detail the design criteria and strategies for some recently reported fluorescent probes that can detect a wide range of biologically important species in cells and in vivo. In doing so, we highlight the importance of each biological species and their role in biological systems and for disease progression. We then discuss the current problems and challenges of existing technologies and provide our perspective on the future directions of the research area. Overall, we hope this review will provide inspiration for researchers and prove as useful guide for the development of the next generation of fluorescent probes.


Assuntos
Corantes Fluorescentes , Biomarcadores
11.
Chem Commun (Camb) ; 58(94): 13103-13106, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36342473

RESUMO

We report on a superoxide anion (O2˙-) responsive fluorescent probe called TCF-OTf. TCF-OTf is able to monitor O2˙- production when the bacterial species Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis are exposed to chloramphenicol and heat shock at 50 and 58 °C.


Assuntos
Corantes Fluorescentes , Superóxidos , Cloranfenicol/farmacologia , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Escherichia coli , Bactérias , Enterococcus faecalis , Resposta ao Choque Térmico
12.
Proc Natl Acad Sci U S A ; 119(43): e2213373119, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36256822

RESUMO

The high level of reactive oxygen species (ROS) in the rheumatoid arthritis (RA) microenvironment (RAM) and its persistent inflammatory nature can promote damage to joints, bones, and the synovium. Targeting strategies that integrate effective RAM regulation with imaging-based monitoring could lead to improvements in the diagnosis and treatment of RA. Here, we report the combined use of small interfering RNAs (siRNAsT/I) and Prussian blue nanoparticles (PBNPs) to silence the expression of proinflammatory cytokines TNF-α/IL-6 and scavenge the ROS associated with RAM. To enhance the in vitro and in vivo biological stability, biocompatibility, and targeting capability of the siRNAsT/I and PBNPs, macrophage membrane vesicles were used to prepare biomimetic nanoparticles, M@P-siRNAsT/I. The resulting constructs were found to suppress tumor necrosis factor-α/interleukin-6 expression and overcome the hypoxic nature of RAM, thus alleviating RA-induced joint damage in a mouse model. The M@P-siRNAsT/I of this study could be monitored via near-infrared photoacoustic (PA) imaging. Moreover, multispectral PA imaging without the need for labeling permitted the real-time evaluation of M@P-siRNAsT/I as a putative RA treatment. Clinical microcomputed tomography and histological analysis confirmed the effectiveness of the treatment. We thus suggest that macrophage-biomimetic M@P-siRNAsT/I and their analogs assisted by PA imaging could provide a new strategy for RA diagnosis, treatment, and monitoring.


Assuntos
Artrite Reumatoide , Nanopartículas , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Microtomografia por Raio-X , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , RNA Interferente Pequeno/uso terapêutico
13.
Chem Commun (Camb) ; 58(76): 10699-10702, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36069107

RESUMO

Aryl boronate fluorescent probes allow the non-invasive study of dynamic cellular processes involving the reactive species, hydrogen peroxide (H2O2) and peroxynitrite (ONOO-). However, the ability of these probes to differentiate between these two species remains unclear. Here, we report a boronate-functionalised hemicyanine dye (HD-BPin) as a potential strategy to distinguish between H2O2 at 704 nm (red channel) and ONOO- at 460 nm (blue channel) in solution and in cells. This work also highlights the choice of fluorophore before boronate functionalization can dictate the observed selectivity between these two species.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Peróxido de Hidrogênio
14.
J Am Chem Soc ; 144(16): 7382-7390, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35421310

RESUMO

Deferasirox, an FDA-approved iron chelator, has gained increasing attention for use in anticancer and antimicrobial applications. Recent efforts by our group led to the identification of this core as an easy-to-visualize aggregation-induced emission platform, or AIEgen, that provides a therapeutic effect equivalent to deferasirox (J. Am. Chem. Soc. 2021, 143, 3, 1278-1283). However, the emission wavelength of the first-generation system overlapped with that of Syto9, a green emissive dye used to indicate live cells. Here, we report a library of deferasirox derivatives with various fluorescence emission profiles designed to overcome this limitation. We propose referring to systems that show promise as both therapeutic and optical imaging agents as "illuminoceuticals". The color differences between the derivatives were observable to the unaided eye (solid- and solution-state) and were in accord with the Commission Internationale de L'Eclairage (CIE) chromaticity diagram 1913. Each fluorescent derivative successfully imaged the respective spherical and rod shapes of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. They also displayed iron-dependent antibiotic activity. Three derivatives, ExNMe2 (3), ExTrisT (11), and ExDCM (13), display emission features that are sufficiently distinct so as to permit the multiplex (triplex) imaging of both MRSA and P. aeruginosa via stimulated emission depletion microscopy. The present deferasirox derivatives allowed for the construction of a multi-fluorophore sensor array. This array enabled the successful discrimination between Gram-positive/Gram-negative and drug-sensitive/drug-resistant bacteria. Antibiotic sensitivity and drug-resistant mutants from clinically isolated strains could also be identified and differentiated.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Deferasirox/farmacologia , Fluorescência , Quelantes de Ferro/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa
15.
Bioact Mater ; 14: 76-85, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35310350

RESUMO

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities. We report here a dual-therapeutic prodrug, DOXjade, that allows for iron chelation chemo-photothermal cancer therapy. This prodrug takes advantage of the clinically approved iron chelator deferasirox (ExJade®) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading DOXjade onto ultrathin 2D Ti3C2 MXene nanosheets produces a construct, Ti 3 C 2 -PVP@DOXjade, that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites, while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%. Antitumor mechanistic investigations reveal that upon activation, Ti 3 C 2 -PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

16.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35193966

RESUMO

Photoacoustic (PA) imaging offers promise for biomedical applications due to its ability to image deep within biological tissues while providing detailed molecular information; however, its detection sensitivity is limited by high background signals that arise from endogenous chromophores. Genetic reporter proteins with photoswitchable properties enable the removal of background signals through the subtraction of PA images for each light-absorbing form. Unfortunately, the application of photoswitchable chromoproteins for tumor-targeted imaging has been hampered by the lack of an effective targeted delivery scheme; that is, photoswitchable probes must be delivered in vivo with high targeting efficiency and specificity. To overcome this limitation, we have developed a tumor-targeting delivery system in which tumor-homing bacteria (Escherichia coli) are exploited as carriers to affect the point-specific delivery of genetically encoded photochromic probes to the tumor area. To improve the efficiency of the desired background suppression, we engineered a phytochrome-based reporter protein (mDrBphP-PCMm/F469W) that displays higher photoswitching contrast than those in the current state of the art. Photoacoustic computed tomography was applied to achieve good depth and resolution in the context of in vivo (mice) imaging. The present system effectively integrates a genetically encoded phytochrome-based reporter protein, PA imaging, and synthetic biology (GPS), to achieve essentially background-suppressed tumor-targeted PA monitoring in deep-seated tissues. The ability to image tumors at substantial depths may enable target-specific cancer diagnoses to be made with greater sensitivity, fidelity, and specificity.


Assuntos
Neoplasias/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Fitocromo/metabolismo , Animais , Linhagem Celular Tumoral , Escherichia coli , Feminino , Genes Reporter/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Molecular/métodos , Fitocromo/farmacologia , Análise Espectral/métodos , Tomografia Computadorizada por Raios X/métodos
17.
Chem Soc Rev ; 51(4): 1212-1233, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35099487

RESUMO

Cancer is the deadliest disease in the world behind heart disease. Sadly, this remains true even as we suffer the ravages of the Covid-19 pandemic. Whilst current chemo- and radiotherapeutic treatment strategies have significantly improved the patient survival rate, disease reoccurrence continues to pose a deadly risk for all too many patients. Incomplete removal of tumour cells from the body increases the chances of metastasis and developing resistance against current treatments. Immunotherapy represents a therapeutic modality that has helped to overcome these limitations in recent decades. However, further progress is needed. So-called immunogenic cell death (ICD) is a recently discovered and unique mode of cell death that could trigger this necessary further progress. ICD involves stimulation of a tumour-specific immune response as a downstream effect. Facilitated by certain treatment modalities, cells undergoing ICD can trigger the IFN-γ mediated immune response involving cytotoxic T cells (CTLs) and γδ T cells that eradicate residual tumour cells. In recent years, there has been a significant increase in the number of small-molecules being tested as potential ICD inducers. A large number of these ICD inducers are metal-based complexes. In fact, anticancer metal drugs based on Pt, Ru, Ir, Cu, and Au are now known to give rise to an immune response against tumour cells as the result of ICD. Advances have also been made in terms of exploiting combinatorial and delivery strategies. In favourable cases, these approaches have been shown to increase the efficacy of otherwise ICD "silent" metal complexes. Taken in concert, rationally designed novel anticancer metal complexes that can act as ICD inducers show promise as potential new immunotherapies for neoplastic disease. This Tutorial Review will allow the readers to assess the progress in this fast-evolving field thus setting the stage for future advances.


Assuntos
Antineoplásicos , COVID-19 , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Morte Celular Imunogênica , Imunoterapia , Neoplasias/terapia , Pandemias , SARS-CoV-2
18.
J Am Chem Soc ; 144(1): 174-183, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34931825

RESUMO

Changes in adenosine triphosphate (ATP) and peroxynitrite (ONOO-) concentrations have been correlated in a number of diseases including ischemia-reperfusion injury and drug-induced liver injury. Herein, we report the development of a fluorescent probe ATP-LW, which enables the simultaneous detection of ONOO- and ATP. ONOO- selectively oxidizes the boronate pinacol ester of ATP-LW to afford the fluorescent 4-hydroxy-1,8-naphthalimide product NA-OH (λex = 450 nm, λem = 562 nm or λex = 488 nm, λem = 568 nm). In contrast, the binding of ATP to ATP-LW induces the spirolactam ring opening of rhodamine to afford a highly emissive product (λex = 520 nm, λem = 587 nm). Due to the differences in emission between the ONOO- and ATP products, ATP-LW allows ONOO- levels to be monitored in the green channel (λex = 488 nm, λem = 500-575 nm) and ATP concentrations in the red channel (λex = 514 nm, λem = 575-650 nm). The use of ATP-LW as a combined ONOO- and ATP probe was demonstrated using hepatocytes (HL-7702 cells) in cellular imaging experiments. Treatment of HL-7702 cells with oligomycin A (an inhibitor of ATP synthase) resulted in a reduction of signal intensity in the red channel and an increase in that of the green channel as expected for a reduction in ATP concentrations. Similar fluorescence changes were seen in the presence of SIN-1 (an exogenous ONOO- donor).


Assuntos
Ácido Peroxinitroso
19.
Chem Commun (Camb) ; 57(86): 11386-11389, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34647549

RESUMO

We report a chemiluminescent probe (CLPT1) that permits the paired detection of tyrosinase (Tyr) and biological thiols. Tyr only leads to a poor chemiluminescence response, a finding ascribed to the formation of a stable o-benzoquinone intermediate. The addition of glutathione (GSH), or ascorbate to the o-benzoquinone intermediate results in thiol conjugation or reduction to this intermediate, respectively. This produces a strong chemiluminescence response. Thiol co-dependence was demonstrated in live cells using the cell permeable analogue, CLPT3. The present chemiluminescence-based strategy allows the concurrent detection of tyrosinase activity and biological thiols.


Assuntos
Corantes Fluorescentes/química , Monofenol Mono-Oxigenase/análise , Compostos de Sulfidrila/análise , Ácido Ascórbico/química , Benzoquinonas/química , Técnicas Biossensoriais , Permeabilidade da Membrana Celular , Glutationa/química , Humanos , Medições Luminescentes , Oxirredução , Relação Estrutura-Atividade
20.
Chem Sci ; 12(33): 11089-11097, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34522306

RESUMO

Triple negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer. Here, we report the construction of graphene nanoribbon (GNR)-based supramolecular ensembles with dual-receptor (mannose and αvß3 integrin receptors) targeting function, denoted as GNR-Man/PRGD, for targeted photothermal treatment (PTT) of TNBC. The GNR-Man/PRGD ensembles were constructed through the solution-based self-assembly of mannose-grafted GNRs (GNR-Man) with a pyrene-tagged αvß3 integrin ligand (PRGD). Enhanced PTT efficacies were achieved both in vitro and in vivo compared to that of the non-targeting equivalents. Tumor-bearing live mice were administered (tail vein) with GNR-Man/PRGD and then each mice group was subjected to PTT. Remarkably, GNR-Man/PRGD induced complete ablation of the solid tumors, and no tumor regrowth was observed over a period of 15 days. This study demonstrates a new and promising platform for the development of photothermal nanomaterials for targeted tumor therapy.

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