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Integrated multi-omics analysis reveals unique signatures of paclitaxel-loaded poly(lactide-co-glycolide) nanoparticles treatment of head and neck cancer cells |
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| Authors: | Mohamed Haider Jayalakshmi Jagal Khuloud Bajbouj Basma M. Sharaf Lina Sahnoon Javan Okendo Mohammad H. Semreen Mawieh Hamda Nelson C. Soares |
| Affiliation: | 1. Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, UAE Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, UAE;2. Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, UAE;3. Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, UAE Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE;4. Systems and Chemical Biology Division, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;5. Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, UAE Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, UAE;6. Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah, UAE Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, UAE |
| Abstract: | The use of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) as carriers for chemotherapeutic drugs is regarded as an actively targeted nano-therapy for the specific delivery of anti-cancer drugs to target cells. However, the exact mechanism by which PLGA NPs boost anticancer cytotoxicity at the molecular level remains largely unclear. This study employed different molecular approaches to define the response of carcinoma FaDu cells to different types of treatment, specifically: paclitaxel (PTX) alone, drug free PLGA NPs, and PTX-loaded PTX-PLGA NPs. Functional cell assays revealed that PTX-PLGA NPs treated cells had a higher level of apoptosis than PTX alone, whereas the complementary, UHPLC-MS/MS (TIMS-TOF) based multi-omics analyses revealed that PTX-PLGA NPs treatment resulted in increased abundance of proteins associated with tubulin, as well as metabolites such as 5-thymidylic acid, PC(18:1(9Z)/18:1(9Z0), vitamin D, and sphinganine among others. The multi-omics analyses revealed new insights about the molecular mechanisms underlying the action of novel anticancer NP therapies. In particular, PTX-loaded NPs appeared to exacerbate specific changes induced by both PLGA-NPs and PTX as a free drug. Hence, the PTX-PLGA NPs’ molecular mode of action, seen in greater detail, depends on this synergy that ultimately accelerates the apoptotic process, resulting in cancer cell death. |
| Keywords: | cancer metabolomics multi-omics proteomics PLGA nanoparticles Paclitaxel |