A biotin-functionalized amphiphilic star-shaped block copolymer, POSS-(PCL-b-PDMAEMA)(8)-biotin,with an inorganic POSS nucleus, a hydrophobic poly(E-caprolactone) (PCL) middle layer, a hydrophilic poly(2(dimethylamino)ethyl methacrylate) (PDMAEMA) outer corona was synthesized for the targeting delivery and pH-responsive release of hydrophobic pheophorbide A (PPa) photosensitizers. In aqueous solution, this amphiphilic copolymer was able to form unimolecular micelles as determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The biotin-functionalized unimolecular micelles were responsive to pH and further utilized in encapsulation and release of PPa for photodynamic therapy (PDT). The PPa release from PPa-loaded unimolecular micelles could be enhanced at acidic condition. Additionally, confocal laser scanning microscopy (CLSM) and flow cytometry results revealed that PPa-loaded tumor-targeted unimolecular micelles could boost the internalization rate in HeLa cells effectively. Moreover, PPa-loaded unimolecular micelles showed low dark toxicity and high PDT efficacy towards HeLa cells according to the 3-(4, 5-dimethylthiazol-2-y1)-2, 5diphenyltetrazolium bromide (MTT) assay. Thus, PPa-loaded POSS-(PCL-b-PDMAEMA)(8)-biotin would have presented the potential application in PDT. (C) 2017 Published by Elsevier Ltd.