Passive targeting can also be achieved by exploiting the microenvironment surrounding tumor cells, which is distinct from the normal cells. Rapidly dividing cancer cells exhibit a high metabolic rate. Tumor cells utilize glycolysis to maintain adequate supply of nutrients and oxygen, thereby resulting in an acidic environment.9 The pH-sensitive nanoparticulate systems are designed to be stable at a physiologic pH of 7.4 but degraded to release active drug in target tissues in which the pH is less than physiologic values, such as in the acidic environment of tumor cells.10 Hyperthermia is implicated in many pathological areas such as human ovarian carcinoma. Thermo-sensitive polymeric system contains polymer that exhibits a low critical solution temperature (LCST) and that tends to precipitate when the temperature is above LCST in the tumor with concomitant release of payload. Localized hyperthermia in tumors can be induced by physical methods such as ultrasound or photothermal means.11,12 Additionally, cancer cells express and release unique enzymes such as matrix metalloproteinases (MMPs), which are implicated in their movement and survival mechanisms.13An albumin-bound form of doxorubicin (DOX) incorporating a MMP-2-specific octapeptide sequence between the drug and the carrier was observed to be efficiently and specifically cleaved by MMP-2 in an in vitro study.14