Long circulating pH-sensitive
liposomes have been shown to effectively deliver
doxorubicin (DOX) to
tumors and reduce its toxic effects.
Folic acid receptors are upregulated in a wide variety of solid, epithelial
tumors, including
breast cancer. In order to improve liposomal endocytosis and antitumor activity,
folic acid has been added to nanoparticles surfaces to exploit overexpression of
folate receptors in
tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive
folate-coated DOX-loaded
liposomes (SpHL-DOX-Fol) in a 4T1
breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher
tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after
intravenous administration was observed in comparision with non-
folate-coated
liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary
metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher
tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX
tumor delivery and reduce dose-limiting toxicity.