Folate-targeted liposomal nitrooxy-doxorubicin: An effective tool against P-glycoprotein-positive and folate receptor-positive tumors

203P-glycoprotein transporter limits the success of doxorubicin-based chemotherapy. Here we produced two different formulations of folic acid-decorated liposomes, carrying a synthetic doxorubicin conjugated with nitric oxide-releasing group, able to inhibit P-glycoprotein efflux. These formulations induced huge folic acid receptor-dependent uptake, high delivery and cytotoxicity of doxorubicin in P-glycoprotein-positive breast cancer cells, and significantly higher anti-tumor effects against folic acid-positive/Pgp-positive breast tumors refractory to free doxorubicin and Caelyx®.