Synthesis of folate targeted theranostic cubosomal platform for co-delivery of bismuth oxide and doxorubicin to melanoma in vitro and in vivo.

Liquid crystalline nanoparticles (LCNPs) have gained much attention in cancer nanomedicines due to their unique features such as high surface area, storage stability, and sustained-release profile. In the current study, a novel LCNP for co-encapsulation of Bi2 O3 and hydrophilic doxorubicin (DOX) was fabricated and functionalized with folic acid (FA) to achieve efficient tumor targeting toward CT-scan imaging and chemotherapy of melanoma in vitro and in vivo. LCNPs Bi2 O3 NPs were prepared using glycerol monooleate-pluronic F-127 (GMO/PF127/water). Firstly, GMO/water were homogenized to prepare LC gel. Then, the stabilizer aqueous solution (PF127/Bi2 O3 /DOX) was added to the prepared LC gel and homogenized using homogenization and ultrasonication. The formulated NPs exhibited superior stability with encapsulation efficiency. High cytotoxicity and cellular internalization of the FA-Bi2 O3 -DOX-NPs were observed in comparison with Bi2 O3 -DOX-NPs and the free DOX in folate-receptor (FR) overexpressing cells (B16 F10 ) in vitro. Moreover, ideal tumor suppression with increased survival rate were observed in tumorized mice treated with FA-Bi2 O3 -DOX-NPs compared to those treated with non-targeted one. On the other hand, the CT-imaging ability of the Bi2 O3 -DOX-NPs was tested inB16 F10 tumor-bearing mice. The obtained data indicated a high potential of the developed targeted theranostic FA-Bi2 O3 -DOX-NPs for diagnostics and treatment of melanoma.