Quantitative multi-Omics analysis of paclitaxel-loaded Poly(lactide-co-glycolide) nanoparticles for identification of potential biomarkers for head and neck cancer

ABSTRACT: 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.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Cultured Cells

DISEASE(S): Cancer

SUBMITTER: Jayalakshmi Jagal  

PROVIDER: ST002248 | MetabolomicsWorkbench | Thu Jul 14 00:00:00 BST 2022

REPOSITORIES: MetabolomicsWorkbench