Summary of Study ST002248
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001436. The data can be accessed directly via it's Project DOI: 10.21228/M83Q6B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002248 |
| Study Title | Quantitative multi-Omics analysis of paclitaxel-loaded Poly(lactide-co-glycolide) nanoparticles for identification of potential biomarkers for head and neck cancer |
| Study Summary | The narrow therapeutic index and significant potential for toxicity of chemotherapeutic drugs are two of the factors that restrict their use. Because of the usage of nanoparticles (NPs) as carriers for chemotherapeutic agents, the therapeutic efficacy of these treatments has been significantly boosted. This was accomplished by increasing the bioavailability of the pharmaceuticals and changing the bio-distribution profile of the drugs. Untargeted metabolomics has recently risen to the forefront as a potentially useful method for better comprehending the growth of tumours and the treatment outcomes of many kinds of cancer cells. In the current study, we used LCMS/MS-based untargeted metabolomics to identify differences in the metabolic profile of head and neck squamous cell carcinomas FaDu that were treated with the anticancer drug paclitaxel (PTX) delivered as free drug versus paclitaxel-loaded poly(lactide-co-glycolide) nanoparticles (PXT-PLGA-NPs). The experimental design consisted of four groups: those treated with DMSO (serving as a control), those treated with drug-free PXT, those treated with PXT-PLGA-NPs, and those treated with PLGA-NPs that lacked PTX. MetaboScape (V4, Bruker Daltonics) was used as the platform for the data analysis, and the results were compared to the Bruker Human Metabolome Data Base (HMDB) spectrum library 2.0. We found a total of 162 metabolites with a high level of confidence ascribed to them. The principal component analysis of the metabolites showed that PTX-free drugs grouped along with PXT-PLGA-NPs, but the control and PLGA-NPs without PXT clustered apart from drug-treated cells but together with each other. In further group pairwise comparisons, it was shown that 37 metabolites were substantially dysregulated (p 0.05) between the PTX-free medication and the PXT-PLGA-NPs. Out of these, it is important to call attention to the metabolites that became more abundant as a result of treatment with PXT-PLGA-NPs. These include 5-Thymidyclic acid with a 7.8-fold change (FC) and 3,4,5-Trimethoxycinnamic acid, both of which have been linked in the past to effective anticancer drug treatment (Quinn et al. 2015; Anantharaju et al. 2017). The findings suggest a more successful anti-drug therapy that makes use of NP, and also indicate a number of metabolites that have the potential to serve as indicators for determining how well an antidrug treatment is working. Our previous findings are consistent with these findings. |
| Institute | University of Sharjah |
| Department | Sharjah institute of medical research |
| Laboratory | Drug Delivery |
| Last Name | Jagal |
| First Name | Jayalakshmi |
| Address | Sharjah |
| jjagal@sharjh.ac.ae | |
| Phone | 0552863009 |
| Submit Date | 2022-07-14 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-07-14 |
| Release Version | 1 |
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Project:
| Project ID: | PR001436 |
| Project DOI: | doi: 10.21228/M83Q6B |
| Project Title: | Quantitative multi-Omics analysis of paclitaxel-loaded Poly(lactide-co-glycolide) nanoparticles for identification of potential biomarkers for head and neck cancer |
| Project Type: | LC-MS/MS |
| Project Summary: | Chemotherapeutic agents are limited by their narrow therapeutic index and high risk for toxicity. The use of nanoparticles (NPs) as carriers for chemotherapeutic agents has considerably increased the therapeutic effect of those drugs by improving their bioavailability and altering their bio-distribution profile. Untargeted metabolomics has emerged as potential approach to understand better tumor progression and treatment outcome of multiple cancer cell types. Herein, we have employed LCMS/MS based untargeted metabolomics to pinpoint differences in metabolic profile of head and neck squamous cell carcinomas FaDu, when treated with anticancer Paclitaxel (PTX) delivered as free drugversus Paclitaxel-loaded poly(lactide-co-glycolide) nanoparticle (PXT-PLGA-NPs). The experimental design include four groups treated with DMSO (control), treated with drug free PXT, PXT-PLGA-NPs and PLGA-NPs without PXT. Data was analyzed using MetaboScape (V4, Bruker Daltonics) platform and matched to Bruker Human Metabolome Data Base (HMDB) spectral library 2.0. We identified and total of 162 high confident assigned metabolites. Principle component analysis of the metabolites revealed that PTX free drug clustered together with PXT-PLGA-NPs, whereas control and PLGA-NPs without PXT clustered away from drug treated cells but apart from each other (see figure below). Further group pairwise comparisons indicated 37 metabolites significantly (p<0.05) dysregulated between PTX free drug and PXT-PLGA-NPs. Of these, it is worthy highlight metabolites that became more abundant with PXT-PLGA-NPs treatment, such as 5-Thymidyclic acid 7. 8 fold change (FC) and 3,4,5-Trimethoxycinnamic acid that have been associated previously associated with effective anticancer drug treatment (Quinn et al. 2015; Anantharaju et al. 2017). The results are in line with our pervious findings supporting a more effective antidrug treatment using NP and we indicate a number of metabolites that are potential markers for monitoring the efficacy antidrug treatment. |
| Institute: | University of Sharjah |
| Department: | Sharjah Institute for Medical Research |
| Laboratory: | Drug Delivery |
| Last Name: | Jagal |
| First Name: | Jayalakshmi |
| Address: | SIMR, Medical Campus, University of Sharjah, 27272, Sharjah |
| Email: | jjagal@sharjah.ac.ae |
| Phone: | +971552863009 |
