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Cell-Membrane Penetration of Tat-Conjugated Polymeric Micelles: Effect of Tat Coating Density.
Macromolecular Bioscience 2019 January 10
Considerable efforts have been devoted to enhancing the cell penetration of nanoparticles by coating cell-penetrating peptides (CPPs) on the surface. However, the internalization mechanism for a CPP at different concentrations varies a lot. It is acknowledged that the mechanism is restricted to endocytic pathway at relatively low concentrations; however, direct translocation becomes dominant at high concentrations. This raises an interesting question on how the surface Tat coating density of the nanoparticles would influence their cell-membrane interaction and the consequent internalization behavior. This study systematically investigates the effect of Tat peptides on the internalization behavior of polymeric micelles by tuning surface Tat coating density, incubation concentrations, incubation time, and other factors using poly(ethylene glycol)-poly(ε-caprolactone) copolymer (PEG-PCL) micelles. It is found that both energy-dependent and energy-independent pathways are involved in the cellular uptake process, and the Tat-conjugated polymeric micelles strongly accumulated on the cell surface at initial stage. The membrane-anchoring and internalization rate increase with the increasing Tat coating density. Furthermore, the increasing of Tat coating density accelerates the energy-independent pathway. It is envisioned that this finding will further shed light on the surface modification of nanoparticles for enhanced cell penetration and direct translocation into cell cytoplasm.
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