Thermally triggered cellular uptake of quantum dots immobilized with poly(n-isopropylacrylamide) and cell penetrating peptide

Thermally sensitive quantum dots (TSQDs) that exhibit an "on-demand" cellular uptake behavior via temperature-induced "shielding/deshielding" of cell penetrating peptides (CPP) on the surface were fabricated. Poly(N-isopropylacrylamide) (PNIPAAm) (M_w = 11.5K) and CPP were biotinylated at their terminal ends and co-immobilized on to the surface of streptavidin-coated quantum dots (QDs-Strep) through biotin-streptavidin interaction. The cellular contact of CPP was sterically hindered due to hydrated PNIPAAm chains below the lower critical solution temperature (LCST). In contrast, above the LCST, grafted PNIPAAm chains were collapsed to make CPP moieties resurfaced, leading to increased cellular uptake of QDs. The temperature-controlled "shielding/deshielding" of CPP was further applied for a thermally triggered siRNA delivery system, where biotinylated siRNA was additionally conjugated to the surface of TSQDs. The level of gene silencing was significantly enhanced by increasing temperature above the LCST due to the surface exposure of CPP.