Cellular Uptake Behavior of Poly(D,L-lactide-co-glycolide) Nanoparticles Derivatized with HIV-1 Tat49-57 Peptide(Abbreviated Title: Tat-PLGA Nanoparticles)

Abstract

This work aims at examining the cellular uptake behavior of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles derivatized with a protein transduction domain (PTD) using HeLa cells. For this purpose, peptide derived from transcriptional activation (Tat) protein of HIV type-1 was covalently conjugated to the terminal end of PLGA. Nanoparticles were ten prepared with the conjugates by a spontaneous phase inversion method. The prepared particles had a mean diameter of ca. 84 nm, as measured by dynamic light scattering. The interaction of the Tat-PLGA nanoparticles with cells was examined by using confocal laser scanning microscopy. It was found tat Tat-PLGA nanoparticles incubated with HeLa cells could efficiently translocate into cytoplasm, while plain PLGA nanoparticles showed negligible cellular uptake. In addition, even at or in the presence of sodium azide significant cellular internalization of Tat-PLGA nanoparticles was still observed. These results indicate that a non-endocytotic translocation mechanism might be involved in the cellular uptake of Tat-PLGA nanoparticles.