Core-shell type of nanoparticles (NPs) with manipulated degradation rate and balanced hydrophilic/hydrophobic properties were designed and characterized. The NPs based on the copolymers of n-butyl cyanoacrylate (BCA) and 2-octyl cyanoacrylate (OCA) were prepared by anion emulsion polymerization in 0.01N HCl solution with pluronic F127 as the stabilizer. These NPs were spherical in shape and with size smaller than 100nm in a narrow distribution. The particle size, zeta potential, molecular weight, hydrophobicity and degradation rate of the copolymer depended on its composition significantly. In vitro chemical hydrolytic studies indicated that the degradation rate of the NPs could be controlled over 200-fold by adjusting the BCA/OCA ratio. Differential scanning calorimetry (DSC) measurements verified the existence of copolymer with tapered structure which was induced by the reactivity difference of the monomers. A BCA/OCA core-shell structure is postulated that the OCA rich segments were mainly located in the core of the NPs. The cytotoxicity of poly(2-octyl cyanoactylate) (POCA) is quite lower than that of poly(n-butyl cyanoacrylate) (PBCA) and the toxicity of poly(BCA-co-OCA) NPs is similar to that of PBCA NPs.