Novel unimolecular micelles from amphiphilic hyperbranched block copolymer H40-poly(epsilon-caprolactone)-b-poly(acrylic acid)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCLb-PAA-b'-MPEG/PEG-FA (HCAE-FA)) as new multifunctional nanocarriers to pH-induced accelerated release and tumor-targeted delivery of poorly water-soluble anticancer drugs were developed. The hydrophobic core of the unimolecular micelle was hyperbranched polyester (H40-poly(epsilon-caprolactone) (H40-PCL)). The inner hydrophilic layer was composed of PAA segments, while the outer hydrophilic shell was composed of PEG segments. This copolymer formed unimolecular micelles in the aqueous solution with a mean particle size of 33 nm, as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). To study the feasibility of micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, paclitaxel (PTX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 10.35 wt.%. In vitro release studies demonstrated that the drug-loaded delivery system is relatively stable at physiologic conditions but susceptible to acidic environments which would trigger the release of encapsulated drugs. Flow cytometry and fluorescent microscope studies revealed that the cellular binding of the FA-conjugated micelles against HeLa cells was higher than that of the neat micelles (without FA). The in vitro cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol (R). All of these results show that these unique unimolecular micelles may offer a very promising approach for targeted cancer therapy. (C) 2014 Elsevier Inc. All rights reserved.