High-density lipoprotein (HDL) nanoparticles were prepared that bore a number of arginine (Arg)-rich peptides (TAT) or related derivatives possessing decreased Arg residues, and their internalization analyzed using three different fluorescent dyes. Substitution of two C-terminal Arg residues of TAT peptide was sufficient to abolish TAT-dependent internalization with HDL, which was essentially the same as the phenomena reported for a single TAT peptide alone. Additionally, high releasability of a dye from the HDLs compensated for this abolishment.