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1.
Talanta ; 275: 126069, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692042

RESUMO

Lipid deposition has been considered one of the key factors in the occurrence of valvular heart disease (VHD) and a great potential target for the diagnosis of VHD. However, the development of lipid imaging technologies and efficient lipid specific probes is in urgent demand. In this work, we have prepared a lipid droplets (LDs) targeted fluorescence probe CPTM based on a push-pull electronic structure for the imaging of diseased aortic valves. CPTM showed obvious twisted intramolecular charge transfer (TICT) effect and its emission changed from 600 nm in water to 508 nm in oil. CPTM not only exhibited good biocompatibility and high photostability, but also impressive LDs specific imaging performance in human primary valvular interstitial cells and human diseased aortic valves. Moreover, the dynamic changes of intracellular LDs could be monitor in real-time after staining with CPTM. These results were expected to offer new ideals for the designing of novel LDs specific probes for further bioimaging applications.


Assuntos
Valva Aórtica , Corantes Fluorescentes , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Imagem Óptica , Gotículas Lipídicas/química , Cor , Valvopatia Aórtica/diagnóstico por imagem , Lipídeos/química , Lipídeos/análise
2.
J Colloid Interface Sci ; 667: 520-528, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38653073

RESUMO

Fluorescent probes that specifically targeting Lipid droplets (LDs) have shown potential in biological imaging. Albeit, their in vivo applications are limited due to the hydrophobicity, low signal-to-noise ratio (SNR) and LDs-specificity. Thus, we designed a novel probe namely MeOND, and a reactive oxygen species (ROS)-responsive nano-platform to improve in vivo LDs-specific imaging. MeOND exhibits a remarkable twisted intramolecular charge transfer (TICT) effect with a strongly enhanced near-infrared emission in low-polarity lipid environment. Also, MeOND demonstrates satisfactory biocompatibility and superior intracellular LDs imaging capabilities. MeOND encapsulated nano-platform (MeOND@PMM) presented favorable water solubility and biocompatibility. MeOND@PMM remains stable in physiological conditions but quickly degrades in the environment of elevated ROS level. The released MeOND could then light up the intracellular LDs in atherosclerotic plaques. The design of the probe and nano-platform is expected to provide a better tool for the scientific research of LDs and LDs-related diseases.


Assuntos
Aterosclerose , Corantes Fluorescentes , Imagem Óptica , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Aterosclerose/diagnóstico por imagem , Aterosclerose/metabolismo , Corantes Fluorescentes/química , Animais , Camundongos , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Nanopartículas/química , Humanos , Tamanho da Partícula , Células RAW 264.7 , Propriedades de Superfície
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 123030, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37354855

RESUMO

Fluorescence imaging techniques have shown remarkable performance in studying the biological functions of lipid droplets (LDs). However, the biological applications of the commercially available LDs probes suffer from insufficient specificity and low signal/noise ratio (SNR). Herein, we presented a novel near-infrared (NIR) lipid activatable fluorescence probe, namely Me2NND, with extremely low emission in water but significantly enhanced emission in the lipid environment. Me2NND presented good biocompatibility and impressive LDs-specific imaging ability in cells and tissues. Moreover, Me2NND has also shown good photostability and it could efficiently locate the distribution of LDs in human pathological samples of aortic aneurysms and fibrocalcific stenotic aortic valves. This study provided a novel turn-on probe Me2NND and would improve the bio-applications of LDs-specific probes.


Assuntos
Aneurisma , Corantes Fluorescentes , Humanos , Valva Aórtica , Gotículas Lipídicas , Imagem Óptica , Lipídeos
4.
Med Oncol ; 40(5): 154, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37079118

RESUMO

ErbB2 is overexpressed in 15-20% of breast cancer, which is associated with malignancy and poor prognosis. We previously reported that ErbB2 supports malignant progression of breast cancer by upregulating lactate dehydrogenase A (LDHA), an important enzyme in glycolysis. However, whether ErbB2 promotes breast cancer progression through other glycolytic enzymes remains unclear. Hexokinase 1 (HK1) and hexokinase 2 (HK2) are the first rate-limiting enzymes of glycolysis and both of them are increased in breast cancer. Here, we aim to investigate whether ErbB2 upregulates HK1 and HK2 and the role of HK1 and HK2 in the malignant progression of ErbB2-overexpressing breast cancer. In current study, we found that the mRNA level of ErbB2 was positively correlated with that of HK1 and HK2, respectively. Moreover, ErbB2 upregulated the protein levels of HK1 and HK2 in breast cancer cells. We also found that both siHK1 and siHK2 significantly inhibited the proliferation, migration and invasion of ErbB2-overexpressing breast cancer cells. Taken together, our findings suggested that ErbB2 promoted the malignant progression of breast cancer cells by upregulating HK1 and HK2, and HK1 and HK2 might serve as promising therapeutic targets for ErbB2-overexpressing breast cancer.


Assuntos
Neoplasias da Mama , Hexoquinase , Humanos , Feminino , Hexoquinase/genética , Hexoquinase/metabolismo , Neoplasias da Mama/patologia , Glicólise/genética , RNA Mensageiro/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 293: 122486, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36801737

RESUMO

Selective labelling of the plasma membrane (PM) by fluorescence imaging techniques enables an intuitive analysis of cell status together with dynamic changes, and therefore is of great value. We herein disclose a novel carbazole-based probe, CPPPy, that shows aggregation-induced emission (AIE) property and is observed to selectively accumulate at the PM of living cells. Benefiting from its good biocompatibility and PM-targeted specificity, CPPPy can light up the PM of cells by high-resolution imaging even at a low concentration of 200 nM. Simultaneously, CPPPy is capable of generating both singlet oxygen and free radical-dominated species upon visible light irradiation, which further induces irreversible growth inhibition and necrocytosis of tumor cells. This study thus provides new insight into the construction of multifunctional fluorescence probes with PM-specific bioimaging and photodynamic therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Fotoquimioterapia/métodos , Luz , Membrana Celular , Imagem Óptica , Oxigênio Singlete , Fármacos Fotossensibilizantes/farmacologia , Neoplasias/tratamento farmacológico
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 122017, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36323086

RESUMO

Visualizing lipid droplets (LDs) using fluorescence imaging is highly desirable for the diagnosis and treatment of atherosclerotic heart diseases. However, the imaging performance of the current commercial lipid probes is unsatisfactory. In this study, we prepared two probes (TTM and MeO-TTM) with aggregation-induced emission (AIE) properties for LD imaging with efficiency. Interestingly, TTM and MeO-TTM showed low emissions in H2O but their emissions were significantly increased in oil. Moreover, TTM and MeO-TTM showed great biocompatibility and intracellular LDs would be specifically illuminated by these probes with good resistance to photobleaching. In addition, TTM and MeO-TTM also exhibited great imaging performance in studying the spatial distribution of LDs in mouse atherosclerotic plaques. This work not only provides a simple tool for studying atherosclerosis but also hopes to enhance the development of fluorescent probes for LDs-specific imaging applications.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Gotículas Lipídicas , Corantes Fluorescentes , Placa Aterosclerótica/diagnóstico por imagem , Imagem Óptica , Aterosclerose/diagnóstico por imagem
7.
Med Oncol ; 40(1): 40, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471172

RESUMO

The incidence of breast cancer ranks at the top of female malignant tumors in China. Metastasis remains the main cause of death among breast cancer patients. The overexpression of ErbB2 is closely related to the metastasis and poor prognosis of breast cancer patients. Therefore, ErbB2 is an important clinical therapeutic target of breast cancer. However, the molecular mechanism of ErbB2 promoting breast cancer metastasis has not been studied clearly. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in catalyzing the conversion of saturated fatty acids (SFAs) into monounsaturated fatty acids (MUFAs). SCD1 is overexpressed in breast cancer, and its overexpression is an indicator of poor prognosis in breast cancer patients. However, the role of SCD1 in ErbB2-overexpressing breast cancer metastasis has not been reported. In this study, we investigated the role of SCD1 in the migration and invasion of ErbB2-overexpressing breast cancer cells and its molecular mechanism. First, we demonstrated that ErbB2 upregulates the expression of SCD1. Second, we found that SCD1 and its catalytic product oleic acid played crucial roles in migration and invasion of ErbB2-overexpressing breast cancer cells. Finally, we found that in breast cancer cells, ErbB2 upregulated SCD1 through lactate dehydrogenase A (LDHA). To sum up, upregulation of SCD1 by ErbB2 via LDHA promotes the migration and invasion of breast cancer cells.


Assuntos
Neoplasias da Mama , Lactato Desidrogenase 5 , Receptor ErbB-2 , Estearoil-CoA Dessaturase , Feminino , Humanos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Movimento Celular , Lactato Desidrogenase 5/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Regulação para Cima , Invasividade Neoplásica
8.
Med Oncol ; 40(1): 5, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36308575

RESUMO

Cerulenin is a fungal metabolite and a specific inhibitor of fatty acid synthase (FASN), which has shown a potential anticancer activity. 20-25% of breast cancer patients with ErbB2-overexpressing develop resistance to treatment. Therefore, it is urgent to find an effective new target for the treatment of ErbB2-overexpressing breast cancer. Our previous study found that cerulenin inhibits the glycolysis and migration of SK-BR-3 cells, but the effect of cerulenin on other malignant phenotypes of breast cancer is still unknown. Furthermore, the mechanism by which cerulenin displays its inhibitory effects is not fully understood. In this study, we systematically investigate the inhibitory effects of cerulenin on proliferation, migration, invasion and glycolysis of ErbB2-overexpressing breast cancer cells and its molecular mechanism. We found that cerulenin obviously suppresses the proliferation, migration, invasion as well as glycolysis. Through bioinformatic analyses, we found that PKM2 might be a target of cerulenin. In addition, ErbB2 and its signaling pathway upregulated PKM2 protein levels. Furthermore, we demonstrated that cerulenin downregulated the protein levels of ErbB2, PKM2 and EMT markers (MMP9, MMP2 and Snail2) in a dose- and time-dependent manner. Finally, the inhibitory of cerulenin on colony formation, migration, invasion and glycolysis, as well as protein levels of EMT markers were rescued by replenishing with PKM2. These findings illustrated that cerulenin inhibits proliferation, migration, invasion and glycolysis by targeting ErbB2/PKM2 pathway in ErbB2-overexpressing breast cancer cells.


Assuntos
Neoplasias da Mama , Cerulenina , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Cerulenina/farmacologia , Cerulenina/metabolismo , Ácido Graxo Sintases/metabolismo , Glicólise , Receptor ErbB-2 , Transdução de Sinais , Neoplasias da Mama/metabolismo , Proteínas de Ligação a Hormônio da Tireoide
9.
Analyst ; 147(13): 3081-3086, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35678714

RESUMO

The dysregulation of lipid droplets (LDs) is closely related to certain metabolic diseases, while the role of LDs during pathological processes remains mysterious. It would be of great value to monitor the dynamic changes of LDs in a visible way so as to study their biological functions. In this study, we report a LD-specific fluorescence probe TBI for precise LD-targeting imaging in cells and atherosclerotic tissues. TBI exhibited great biocompatibility, remarkable oil-enhanced fluorescence emission, good photostability and impressive intracellular and tissular LD-specific imaging performance. Importantly, TBI could efficiently stain the LDs at a low concentration of 50 nM, and the motion tracking of LDs could be observed via fluorescence imaging. Moreover, TBI could efficiently light up the LD distribution in mouse atherosclerotic plaques with high resolution, which revealed the ultra-structure of atherosclerotic plaques. In conclusion, these results imply that TBI could be a potential tool for investigating the physiological and pathological role of LDs.


Assuntos
Gotículas Lipídicas , Placa Aterosclerótica , Animais , Corantes Fluorescentes/química , Gotículas Lipídicas/metabolismo , Camundongos , Imagem Óptica , Placa Aterosclerótica/diagnóstico por imagem
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 271: 120895, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35065518

RESUMO

Lipid droplets (LDs) have been regarded as potential marker for study the pathologic processes and diagnosis of valvular heart disease. While conventional imaging strategy fail to precisely locate LDs in pathological tissues. Herein, a LDs specific probe ECPID with special feature of single-excitation but dual-emission in oil (520 nm) and water (628 nm) was prepared for LDs imaging. ECPID exhibited good biocompatibility, great performance in intracellular and tissular LDs imaging, which would help to reveal the pathologic process of human fibrocalcific aortic valvular leaflet. Our work offers a novel approach for accurate imaging LDs in situ and paves a way to study the pathologic processes of valvular disease.


Assuntos
Gotículas Lipídicas , Água , Diagnóstico por Imagem , Corantes Fluorescentes , Humanos
11.
J Mater Chem B ; 9(19): 4050-4055, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33949611

RESUMO

Fluorescence imaging plays an important role in researching the biological function of lipid droplets (LDs). However, the short-wave emission, tedious synthesis process and insufficient specificity have significantly limited the applications of commercially available probes. Herein, we have prepared a novel one-step synthesized near-infrared (NIR) fluorescent probe, TNBD, with a very low emission in aqueous solution and the solid state, but a significantly enhanced fluorescence emission is exhibited in oleic acid. Moreover, TNBD exhibited an impressive lipid droplet (LD) specific fluorescence turn-on ability in cells, fatty liver and atherosclerosis (AS) samples with a good biocompatibility and high signal-to-noise ratio. Our study not only establishes a novel LD turn-on fluorescence probe, but also provides a novel way to prepare a NIR LD targeted fluorescence probe.


Assuntos
Aterosclerose/diagnóstico por imagem , Fígado Gorduroso/diagnóstico por imagem , Corantes Fluorescentes/química , Gotículas Lipídicas/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Microscopia Confocal , Células RAW 264.7 , Razão Sinal-Ruído , Espectroscopia de Luz Próxima ao Infravermelho
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