[Show abstract][Hide abstract] ABSTRACT: Biomimetic acryloyloxyethyl phosphorylcholine (APC) was used to react with generation 5 poly(amido amine) (PAMAM) dendrimers (G5) via the Michael addition reaction between primary amino group of PAMAM dendrimers and acrylic functional group of APC. FTIR and (1)H NMR confirmed the success of surface modification of G5. The primary amino and phosphorylcholine (PC) group numbers of the surface engineered PAMAM dendrimers (G5-PC) were calculated to be 56 and 50 via (1)H NMR and potentiometric titration. Cell viability and cell morphology studies indicated that biomimetic phosphorylcholine surface engineering successfully lowered the cytotoxicity of G5 PAMAM dendrimers. The hydrophobic interior of G5-PC was used to incorporate anti-cancer drug Adriamycin (ADR) and the G5-PC showed sustained releasing behavior for ADR. Cell morphology and viability tests indicated that the drug-loaded G5-PC conjugate could effectively enter the cancer cells and inhibit the growth of cancer cells. Biomimetic phosphorylcholine surface engineered PAMAM dendrimers with lowered cytotoxicity and high cellular penetrating ability showed great potential for the biomedical applications as nanocarrier system.