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Folic Acid-Functionalized Gold Nanorods for Controlled Paclitaxel Delivery: In Vitro Evaluation and Cell Studies

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Abstract

Short gold nanorods were synthesized (average length 28.08 nm, average aspect ratio 3.54), which were functionalized with folic acid (FA) and 8-mercaptooctanoic acid (MOA) or 11-mercaptoundecanoic acid (MDA) and loaded with paclitaxel (PCT). FA was conjugated to the nanorods in order to render them targetable for cancer cells overexpressing folate receptors whereas MOA or MDA was attached on the nanorods in order to generate extra hydrophobic areas for entrapment of hydrophobic drugs such as PCT in the nanorods and in order to provide free carboxylic groups, which would allow for the conjugation of drug or other biofunctional molecules to the nanorods. The functionalized gold nanorods (GNRs-MOA-FA and GNRs-MDA-FA) did not exhibit any significant degree of aggregation in cell culture medium and blood plasma even after a prolonged incubation period of 7 days, indicating the adequate colloidal stability of the nanorods in these media. The functionalized nanorods exhibited satisfactory entrapment efficiency (around 40%) for PCT and released less than 25% of their PCT content in phosphate buffer pH 7.4 in 48 h. PCT entrapment efficiency was a little higher and PCT release rate a little lower in the GNRs-MOA-FA. Molecular analysis (qPCR) was used to find out that the MDA-MB-231 cancer cell line expresses the folate receptor (FL1R) whereas the MCF-7 cancer cell line does not. The PCT-loaded GNRs-MOA-FA were more cytotoxic than the PCT-loaded GNRs-MOA nanorods against the MDA-MB-231 cells, which probably relates to the higher uptake of the GNRs-MOA-FA nanorods by these cells. The opposite was true in the case of the MCF-7 cells.

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Acknowledgements

The authors thank Dr. Maria Kollia from the Laboratory of Electron Microscopy and Microanalysis at the University of Patras for the TEM images.

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Authors and Affiliations

  1. Department of Pharmacy, School of Health Sciences, University of Patras, Patras, 265 04, Rio, Greece

    Ligeri Papaioannou, Athina Angelopoulou, Sophia Hatziantoniou & Konstantinos Avgoustakis

  2. Research Genetic Cancer Centre S.A., Industrial Area of Florina, 531 00, Florina, Greece

    Maria Papadimitriou, Panagiotis Apostolou & Ioannis Papasotiriou

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  1. Ligeri Papaioannou
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  2. Athina Angelopoulou
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Correspondence to Konstantinos Avgoustakis.

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Papaioannou, L., Angelopoulou, A., Hatziantoniou, S. et al. Folic Acid-Functionalized Gold Nanorods for Controlled Paclitaxel Delivery: In Vitro Evaluation and Cell Studies. AAPS PharmSciTech 20, 13 (2019). https://doi.org/10.1208/s12249-018-1226-6

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