AbstractWe have synthesized core-multishell (CMS) nanocarriers with different outer shells and the self-aggregation behavior and the transport capacity of these nanocarriers were studied with the hydrophobic guest molecules Nile red (NR) and methotrexate (MTX). The outer shell either consisted of methoxypoly(ethylene glycol) (mPEG) or polyglycerol (PG) dendrons of generation one or two. NR was solubilized by all CMS nanocarriers. The solubilization of MTX could only be achieved with mPEG-terminated CMS nanocarriers. Depending on the encapsulated guest, the CMS nanocarriers showed self-aggregation. The NR loaded CMS nanocarriers all formed bigger aggregates with a radius between 110 and 170 nm. In the case of the MTX loaded CMS nanocarriers, the MTX prevented the formation of CMS aggregates and therefore its efficient transport