pH-sensitive PEGylated liposomes for tumor cell targeting

The tumour tissue displays peculiar features, namely altered pH, temperature, redox potential and enzymatic pool, that can be exploited to yield site directed nanocarriers, namely liposomes. In particular, the pH of solid tumors is lower than in normal tissues. Therefore, it is convenient to trigger the response of adequately designed systems that can undergo morphological changes when exposed to the microenvironment alteration (1, 2). Based on the peculiar features of tumor tissues and the drug delivery properties of liposomes, we investigated a novel class of pH-sensitive nanocarriers for anticancer drug delivery that can undergo structural changes under pathophysiological microenvironmental conditions thus providing for selective drug targeting. pH sensitive liposomes were obtained by surface decoration with stearoyl-PEG-poly-sulfadimethoxine (stearoyl-PEG-poly(SDM) that has been previously found to sense the pH decrease. Indeed, the acid character of sulfadimethoxine (pKa of 6.1) promotes the pH induced hydrophilic/hydrophobic switching as consequence of protonation, which may occur in the tumour site (3). Such physical alteration of the pH sensor stearoyl-PEG-poly-sulfadimethoxine is expected to be transferred to the surface properties of the nanocarriers, which may finally promote the interaction of the carrier with the cells or prompt the drug release.