Novel double hydrophilic poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA) synthesized via free radical polymerization of corresponding monomers with defined molar ratios in the presence of K2S2O8 as an initiator in an aqueous solution. The resulting copolymer was subsequently converted to a cholesterol conjugate (PMMICholC6-co-PDMAEMA) by esterification reaction with 6-cholesteryl-1-hexanol (CholC6). Two copolymers self-assembled into micelles by simply adjusting the solution pH at room temperature. The non-conjugated polymer had a sharp transition at pH 5. TEM and DLS studies showed that both micelles were spherical in shape with a mean diameter around 85 and 26 nm, respectively. Piroxicam (PX) as a hydrophobic model drug was encapsulated into micelles. The results indicated that PMMICholC6-co-PDMAEMA micelles were able to load more amounts of drug than PMMI-co-PDMAEMA micelles which could be attributed to the strong hydrophobic interactions of cholesterol molecules in the core. In vitro release studies demonstrated that PX release from PMMI-co-PDMAEMA micelles was significantly fast at physiological pH compared with mildly acidic pH 4.5. However, at pH 4.5, PMMICholC6-co-PDMAEMA micelles, with core-shell-corona structure, released loaded drug molecules faster than pH 7.4 which contained a relatively steady drug release profile. In summary, cholesterol-modified micelles could be introduced as stable and effective pH responsive nanocarriers to make a promising system for enhancing the efficacy of hydrophobic drugs in cancer cells for improved cancer therapy.