Enhanced anti-angiogenic effects of aprepitant-loaded nanoparticles in human umbilical vein endothelial cells


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Kaya Tilki E., Öztürk A. A., Engür Öztürk ., Dikmen M.

SCIENTIFIC REPORTS, vol.14, no.19837, pp.1-17, 2024 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 14 Issue: 19837
  • Publication Date: 2024
  • Doi Number: 10.1038/s41598-024-70791-y
  • Journal Name: SCIENTIFIC REPORTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.1-17
  • Anadolu University Affiliated: Yes

Abstract

Recent advancements in cancer therapy have led to the development of novel nanoparticle-based drug delivery systems aimed at enhancing the efficacy of chemotherapeutic agents. This study focuses on evaluating aprepitant-loaded PLGA and Eudragit RS 100 nanoparticles for their potential antiangiogenic effects. Characterization studies revealed that aprepitant-loaded nanoparticles exhibited particle sizes ranging from 208.50 to 238.67 nm, with monodisperse distributions (PDI < 0.7) and stable zeta potentials (between − 5.0 and − 15.0 mV). Encapsulation efficiencies exceeding 99% were achieved, highlighting the efficacy of PLGA and Eudragit RS 100 as carriers for aprepitant. Cellular uptake studies demonstrated enhanced internalization of aprepitant-loaded nanoparticles by HUVEC cells compared to free aprepitant, as confirmed by fluorescence microscopy. Furthermore, cytotoxicity assays revealed significant dose-dependent effects of aprepitant-loaded nanoparticles on HUVEC cell viability, with IC50 values at 24 h of 11.9 µg/mL for Eudragit RS 100 and 94.3 µg/mL for PLGA formulations. Importantly, these nanoparticles effectively inhibited HUVEC cell migration and invasion induced by M2c supernatant, as evidenced by real-time cell analysis and gene expression studies. Moreover, aprepitant-loaded nanoparticles downregulated VEGFA and VEGFB gene expressions and reduced VEGFR-2 protein levels in HUVEC cells, highlighting their potential as antiangiogenic agents. Overall, this research underscores the promise of nanoparticle-based aprepitant formulations in targeted cancer therapy, offering enhanced therapeutic outcomes through improved drug delivery and efficacy against angiogenesis.