Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 60, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2020.101928
Keywords
Epidermal growth factor receptor; Temozolomide; Polylactic-co-glycolic acid; Cetuximab; Polymeric nanoparticles; Targeted cancer therapy
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF2018R1D1A1B07040858, NRF-2016R1A6A1A03011325]
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Targeted cancer therapy was designed to minimize the different challenges of cancer chemotherapies such as resistance to treatment and systemic toxicity. Epidermal growth factor receptor (EGFR) overexpression is the main factor that causes uncontrolled cancer cell growth. Accordingly, targeting EGFR using anti-EGFR conjugated polymeric nanoparticles (NPs) offers a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In this study, cetuximab (Cmab) was conjugated to temozolomide (TMZ) loaded poly(lactic-co-glycolic acid) NPs (PLGA-NPs), termed as (Cmab-TMZ-PLGA-NPs) by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (NHS) cross-linking chemistry to target EGFR receptor. The physicochemical characteristics of PLGA-NPs, TMZ-PLGA-NPs, and Cmab-TMZ-PLGA-NPs were determined. Furthermore, in vitro cellular uptake of the drug via EGFR receptor-mediated endocytosis by Cmab-TMZ-PLGA-NPs, cell cytotoxicity, apoptosis in U-87MG, SW480, and SK-Mel 28 cancer cell lines was examined. Besides, the upregulation -H2A.X generated by PLGA-gamma NPs, TMZ-PLGA-NPs, and Cmab-TMZ-PLGA-NPs was explored by Western blot assay. Also, a comparative analysis of all results was performed to evaluate the effectiveness of Cmab-TMZ-PLGA-NPs between three cell lines. The study demonstrated that Cmab-TMZ-PLGA-NPs has a superior cellular uptake, higher cytotoxicity, higher apoptotic effect, and upregulated gamma-H2A. X compared to TMZ-PLGA-NPs and free TMZ in U-87MG then SW480 and followed by SK-Mel 28 as a result of high EGFR overexpression. These results confirmed that Cmab conjugated PLGA-NPs offer a versatile nanoplatform for the treatment of EGFR overexpressing cancers.
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