Novel fluorescein isothiocyanate (FITC) cored PAMAM dendrimers as drug delivery agent

Bukun Y., Zaim M., Senel M., Sagir T., Kiyak B. Y., Isık S.

International Journal of Polymeric Materials and Polymeric Biomaterials, cilt.73, sa.10, ss.917-925, 2024 (SCI-Expanded, Scopus)

Özet

Fluorescent dyes, or fluorophores, enable researchers to visualize specific biological molecules by fluorescence microscopy. Herein, a novel fluorescent FITC-poly(amidoamine) (FITC-PAMAM) dendrimers have been synthesized via divergent approach. The molecular structure of the FITC-PAMAM dendrimers (G-0 to G5) was characterized by 1H NMR, 13C NMR spectroscopy and by FTIR. In order to emphasize the structural efficacy of FITC-PAMAM dendrimer, the drug delivery behavior has been evaluated by using 5-fluorouracil (5-FU) as a model cancer therapy drug. Anti-proliferative activity of FITC-cored PAMAM dendrimers in all generations (G0-G5) with or without 5-FU were analyzed on human gastric carcinoma cells (AGS) by WST-1 cell proliferation assay. Initially, the nontoxic dose of unloaded FITC-PAMAM dendrimers was assessed for further drug loading experiments. Loading of 5-FU into FITC-PAMAM dendrimers, regardless of generation, increased the toxicity of the drug. Besides, 5-FU loaded FITC-PAMAM dendrimers induced a generation-based gradual inhibition of cell proliferation. FITC and phase contrast merged images indicated that FITC-PAMAM dendrimers facilitate the entry of the drug into the cells, in a generation-dependent manner. The FITC- dendrimers may serve as a promising intracellular drug delivery agent for 5-FU by increasing cell uptake into cells and thereby, enhancing antiproliferative activity on AGS cells in a generation-dependent manner.