Transferrin-Modified Nanoliposome Codelivery Strategies for Enhancing the Cancer Therapy

Chemotherapy remains one of the most effective treatments for many cancers in a clinic. At present, various targets have been used to modify the PEGylated liposomes for doxorubicin (Dox) delivery, but the antitumor effect of Dox is not satisfactory. Therefore, combination chemotherapeutics has been considered as a promising method to improve tumor treatment. These years, RAF/MEK/ERK-mediated cell signaling pathway has been discovered to inhibit the growth of tumors. Thus, Sorafenib tosylate (Sor) was used in this study, which directly inhibited tumor cell proliferation through blocking RAF/MEK/ERK-mediated cell signaling pathway and indirectly inhibited tumor cell growth through blocking angiogenesis by VEGFR and PDGF. In this article, we develop a "combination delivery system" to deliver the hydrophobic drug (Sor) in phospholipid bilayer and hydrophilic drug (Dox) in inner cores for enhancing the antitumor effect. Moreover, in vitro experiments verified whether the physicochemical properties of carriers were stable and transferrin-modified liposomes displayed the highest uptake. The results of in vivo experiments showed that the codelivery system inhibited the tumor growth more effectively than monotherapy. Overall, this combination delivery system for delivering the hydrophobic and hydrophilic drugs simultaneously may offer a novel strategy for breast cancer treatment and provide a reference for the possibility of clinical usage.