Anticancer research · 2009
Biotinylated poly(amido)amine (PAMAM) dendrimers as carriers for drug delivery to ovarian cancer cells in vitro.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Yellepeddi Venkata K, Kumar Ajay, Palakurthi Srinath
Аннотация
BACKGROUND: Biotin is an essential micronutrient and its levels are high in rapidly proliferating cells such as cancer cells. We hypothesized that the synthesis of poly (amido)amine (PAMAM) dendrimers with biotin molecules might contribute to enhanced cancer cell-specific uptake.
MATERIALS AND METHODS: PAMAM dendrimers were biotinylated using sulfo-NHS-LC-biotin and structural characterization was performed using 1H NMR and matrix assisted laser desorption ionization--time-of-flight. The effect of generation and the mechanism of cellular uptake of biotin-PAMAMG4 in ovarian cancer (OVCAR-3) and human embryonic kidney (HEK 293T) cells was determined by fluorescent microscopy and flow cytometry.
RESULTS: The cellular uptake of Biotin-PAMAM was significantly higher in the OVCAR-3 cells as compared to the HEK 293T cells (p<0.05). While the presence of either free biotin or colchicine significantly reduced the extent of uptake of biotin-PAMAMG4 at lower concentration (0.1 microM). The results demonstrated that the biotinylated-PAMAM was internalized by biotin receptor-mediated endocytosis and charge-mediated adsorptive endocytosis. The cytotoxicity of biotinylated-PAMAMG4 in the HEK 293T cells was comparable to that of the parent PAMAM dendrimers.
CONCLUSION: Biotinylated PAMAM dendrimers show potential as nanocarriers in targeted drug delivery.
MATERIALS AND METHODS: PAMAM dendrimers were biotinylated using sulfo-NHS-LC-biotin and structural characterization was performed using 1H NMR and matrix assisted laser desorption ionization--time-of-flight. The effect of generation and the mechanism of cellular uptake of biotin-PAMAMG4 in ovarian cancer (OVCAR-3) and human embryonic kidney (HEK 293T) cells was determined by fluorescent microscopy and flow cytometry.
RESULTS: The cellular uptake of Biotin-PAMAM was significantly higher in the OVCAR-3 cells as compared to the HEK 293T cells (p<0.05). While the presence of either free biotin or colchicine significantly reduced the extent of uptake of biotin-PAMAMG4 at lower concentration (0.1 microM). The results demonstrated that the biotinylated-PAMAM was internalized by biotin receptor-mediated endocytosis and charge-mediated adsorptive endocytosis. The cytotoxicity of biotinylated-PAMAMG4 in the HEK 293T cells was comparable to that of the parent PAMAM dendrimers.
CONCLUSION: Biotinylated PAMAM dendrimers show potential as nanocarriers in targeted drug delivery.
Предметные рубрики MeSH
Biocompatible MaterialsBiological TransportBiotinBiotinylationCell ProliferationCells, CulturedDendrimersDrug CarriersDrug Delivery SystemsEndocytosisFemaleFlow CytometryFluorescenceHumansKidneyMagnetic Resonance SpectroscopyOvarian NeoplasmsPolyaminesSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSuccinimidesTissue Distribution