The preparation of pH responsive, biodegradable, biocompatible and cross-linked polymer capsules for controlled drug release is presented. These capsules were prepared using silica particles as templates for surface grafting of poly (acrylic acid) (PAA) and PAA-co-poly(polyethylene glycol) acrylate) (PAA-PPEGA) block copolymer via reversible addition fragmentation chain transfer (RAFT) polymerization directly from silica particles, followed by cross-linking with cystamine dihydrochloride and removal of the silica template in the presence of hydrofluoric acid, respectively. The resultant polymer capsules were water soluble, biocompatible with a mean diameter of approximately 260 +/- 10 nm, and non-toxic to human cells at low concentration, which are favorable to be utilized as drug carriers for pH responsive and biodegradation controlled drug release. Doxorubicin hydrochloride (DOX) was chosen as a model drug to test the drug loading and releasing properties of the polymer capsules. It was found that the DOX could be effectively loaded into the PAA and PAA-PPEGA capsules with a loading capacity up to 52.24% and 36.74%, respectively. The pH and biodegradation controlled release behaviors of DOX loaded PAA-PPEGA capsules were also explored. The results imply that both PAA and PAA-PPEGA capsules are promising platforms for pH and biodegradation controlled drug delivery systems, while the PAA-PPEGA capsules exhibit less cytotoxicity. (C) 2014 Elsevier B.V. All rights reserved.