Biocompatible fluorescent probe for detecting mitochondrial alkaline phosphatase activity in live cells

Khatun, Sabina; Biswas, Shayeri; Mahanta, Arun Kumar; Joseph, Manu M.; Vidyalekshmi, Murukan S.; Podder, Arup; Maiti, Pralay; Maiti, Kaustabh Kumar; Bhuniya, Sankarprasad

doi:10.1016/j.jphotobiol.2020.112043

Cited by 8 publications

(6 citation statements)

References 54 publications

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“…[6,7] Recently, the presence and role of ALP in various cancers and diseases have been in the spotlight leading to the development of new ALP detection techniques, disease treatment, as well as diagnostic approaches. [8][9][10][11][12][13][14][15][16][17] Within this review, we aimed to provide an overview about ALP-responsive novel pharmaceutical excipients, drug delivery systems, and diagnostics by also giving a perspective about the distribution (Figure 1) and activity of ALP in the body as well as its specificity and mode of action. Accordingly, the potential of phosphorylated excipients for drug delivery and diagnostics is highlighted.…”

Section: Introductionmentioning

confidence: 99%

Alkaline Phosphatase: A Reliable Endogenous Partner for Drug Delivery and Diagnostics

Le‐Vinh

Akkuş‐Dağdeviren

et al. 2022

Advanced Therapeutics

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Since the 1960s the membrane-bound enzyme alkaline phosphatase (ALP) has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. Anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the target site as due to an ALP-triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. Moreover, features such as the accumulation of nanocarriers at the target site or a targeted drug release triggered by ALP can be introduced. In addition, ALP is utilized to improve the potential of numerous diagnostic systems. Within this review, one provides an overview about the activity, selectivity, and distribution of this enzyme, as well as the great variety of applications in drug delivery and diagnostics making use of it.

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Section: Introductionmentioning

confidence: 99%

Alkaline Phosphatase: A Reliable Endogenous Partner for Drug Delivery and Diagnostics

Le‐Vinh

Akkuş‐Dağdeviren

et al. 2022

Advanced Therapeutics

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“…The study of Morciano et al [ 9 ] showed that mitochondrial dysfunction can promote the synthesis of collagen matrix and alkaline phosphatase of VICs and accelerate the calcification process of CAVS. The study of Khatun et al [ 10 ] indicated that the disorder of mitochondrial metabolism may accelerate the synthesis of alkaline phosphatase and the osteogenic-like changes of VICs. The above researches fully confirmed that the mitochondrial quality imbalance in VICs has important regulatory significance for the occurrence and development of CAVS.…”

Section: Introductionmentioning

confidence: 99%

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis

Liu

Cao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Calcific aortic valve stenosis (CAVS) is the most common heart valve disorder among humans. To date, no effective method has been identified to prevent this disease. Herein, we aimed to identify novel diagnostic and mitochondria-related biomarkers of CAVS, based on two machine learning algorithms. We further explored their association with infiltrating immune cells and studied their potential function in CAVS. The GSE12644, GSE51472, and GSE83453 expression profiles were downloaded from the Gene Expression Omnibus (GEO) repository. The GSE12644 and GSE51472 datasets were integrated to identify differentially expressed genes (DEGs). GSE12644 contains 10 normal and 10 CAVS samples, whereas GSE51472 contains 5 normal and 10 CAVS samples. GO and KEGG assays of DEGs were conducted, and the correlation between matrix metalloproteinase 9 (MMP9) expression and immune cell infiltration was explored, using CIBERSORT. The LASSO regression model and SVM-RFE analysis were used to identify diagnostic genes. The expression of MMP9 in CAVS and non-CAVS samples was measured using RT-PCR, western blotting and immunohistochemistry. A series of functional experiments were performed to explore the potential role of MMP9 in mitochondrial metabolism and oxidative stress during CAVS progression. Twenty-two DEGs were identified, of which six genes (SCG2, PPBP, TREM1, CCL19, WIF1, and MMP9) were ultimately distinguished as diagnostic genes in CAVS. Of these, MMP9 was indicated as a mitochondria-related gene, the expression and diagnostic value of which were further confirmed in the GSE83453 dataset. Correlation analysis revealed a positive correlation between MMP9 and infiltrating immune cells. In our cohort, MMP9 expression was distinctly increased in CAVS samples, and its inhibition attenuated the calcification of valve interstitial cells (VICs) by suppressing mitochondrial damage and oxidative stress. Taken together, our findings suggest MMP9 as a novel mitochondrial dysfunction biomarker and therapeutic target for CAVS.

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“…In this work, the diethyl-phosphate moiety was retained in the molecule to enhance the cellular uptake, instead of the conventional negatively charged free phosphate terminus. Khatun et al reported coumarin-tethered triphenylphosphonium salt ALP-24 for the recognition of (Figure 52) mitochondrial ALP in cellular conditions [91]. The rationale was based on a receptor-fluorophore-subcellular targeting group where coumarin acts as a signaling unit (blue fluorophore), in which the ALP receptor (diethyl phosphate) is attached to the 8 th position, and the mitochondrial targeting moiety triphenylphosphine is connected to a coumarin unit through the ethyl spacer.…”

Section: Or Peer Review 36 Of 60mentioning

confidence: 99%

Recent Advancements in Developments of Novel Fluorescent Probes: In Cellulo Recognitions of Alkaline Phosphatases

et al. 2022

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Alkaline phosphatase (ALP) is one of the vital phospho-ester bond cleaving biocatalysts that has inevitable significance in cellular systems, viz., early-stage osteoblast differentiation, cell integrity in tissues, bone mineralization, cancer biomarker, liver dysfunction, cellular osmotic pressure, protein folding and many more. Variation from optimal levels of ALP in intra and extracellular fluids can cause severe diseases, including death. Due to these reasons, ALP is considered as a vital biomarker for various preclinical and medical diagnosis. Fluorescence image-based diagnosis is the most widely used method, owing to its simplicity, robustness, non-invasive properties and excellent spatio-temporal resolution (up to the nM/pM level), as compared to conventional analytical techniques, such as the electroanalytical method, nuclear magnetic resonance (NMR) and high-performance liquid chromatography (HPLC). Most of the reviews reported for ALP’s recognition in the literature scarcely explain the structurally related, photophysical and biophysical parameters; and the sub-cellular localizations. Considering these facts, in order to enhance the opto-analytical parameters of fluorescence-based diagnostic materials at the cellular level, herein we have systematically documented recent developments in the opto-analytical capabilities of quencher-free probes for ALP, used in in vitro (biological buffers) to in cellulo conditions, along with in vivo models.

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Biocompatible fluorescent probe for detecting mitochondrial alkaline phosphatase activity in live cells

Cited by 8 publications

References 54 publications

Alkaline Phosphatase: A Reliable Endogenous Partner for Drug Delivery and Diagnostics

Alkaline Phosphatase: A Reliable Endogenous Partner for Drug Delivery and Diagnostics

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis

Recent Advancements in Developments of Novel Fluorescent Probes: In Cellulo Recognitions of Alkaline Phosphatases

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