Hybrid Theranostic Cubosomes for Efficient NIR-Induced Photodynamic Therapy

[Image: see text] In recent years, lipid bicontinuous cubic liquid-crystalline nanoparticles known as cubosomes have been under investigation because of their favorable properties as drug nanocarriers useful for anticancer treatments. Herein, we present organic/inorganic hybrid, theranostic cubosomes stabilized in water with a shell of alternate layers of chitosan, single strand DNA (model genetic material for potential gene therapy), and folic acid–chitosan conjugate (the outmost layer), coencapsulating up-converting Er(3+) and Yb(3+) codoped NaYF(4) nanoparticles and daunorubicin. The latter acts as a chemotherapeutic drug of photosensitizing activity, while up-converting nanoparticles serve as energy harvester and diagnostic agent. Cellular uptake and NIR-induced photodynamic therapy were evaluated in vitro against human skin melanoma (MeWo) and ovarian (SKOV-3) cancer cells. Results evidenced the preferential uptake of the theranostic cubosomes in SKOV-3 cells in comparison to uptake in MeWo cells, and this effect was enhanced by the folic acid functionalization of the cubosomes surface. Nanocarriers coloaded with the hybrid fluorophores exhibited a superior NIR-induced photodynamic activity, also confirmed by the improved mitochondrial activity and the most affecting f-actin fibers of cytoskeleton. Similar results, but with higher photocytotoxicity, were detected when folic acid-functionalized cubosomes were incubated with SKOV-3 cells. Taken on the whole, these results prove these hybrid cubosomes are good candidates for the photodynamic treatment of tumor lesions.