Glucose and Transferrin Liganded PLGA Nanoparticles Internalization in Non-Small Lung Cancer Cells

Abstract

Introduction: Recently, after a decade of confusing results, several studies pointed out that overexpression of GLUT1 (glucose transporter 1) is a biomarker of worse prognosis in NSCLC. Nonetheless, the presence of transferrin (Tf receptor), which is overexpressed in most cancer tissues and most lung cancers as well, in NSCLC is also an indicator of very poor prognosis. Therefore, these ligands can be used for active targeting of lung cancer cells and improved efficacy of internalization of cancer therapy using nanomedicines. Objectives: Having the background, the main goal of the project was the assessment of the influence of the glucose and transferrin ligands on the efficacy of internalization of the designed (i) glucose decorated PLGA (poly lactic-coglycolic acid) nanoparticles (Glu-PLGA NPs) and (ii) transferrin decorated PLGA nanoparticles (Tf-PLGA NPs) in comparison to (iii) non-liganded PLGA NPs using a A549 lung cancer cells. Methods: Glu-PLGA NPs, Tf-PLGA NPs and PLGA NP - fluorescently labelled), were designed using a sonication assisted nanoprecipitation method. Further, physicochemical properties characterization (particle size analysis, zeta potential, FTIR analysis, DSC analysis), cytotoxicity evaluation using MTT test, and cell internalization studies of DTAF labelled NPs using fluorimetry in A549 NSCLC cell line were performed. Results: The results pointed to a significantly improved internalization rate of the liganded compared to PLGA NPs. Glu-PLGA NPs showed higher internalization rate compared to Tf-PLGA and PLGA NPs, in the serum-supplemented and serumfree medium even at normal levels of glucose in the cell growth medium. Conclusion: The developed nanocarriers offer unique advantages of enhanced targetability, improved cell internalization and decreased toxicity, which makes them promising solution for current therapeutic limitations.