"Biotin-targeted mixed liposomes: A smart strategy for selective release of a photosensitizer agent in cancer cells"

Abstract

The high incidence of cancer, necessity of treatment, and prognosis times are urgent issues that need to be addressed. In this work, we present DPPC liposomes coated with F127 triblock copolymers as a promising alternative in drug delivery systems for cancer therapy. The proposed mixed liposomes exhibit adequate size, high stability, and passive targeting that result from the EPR effect. An interesting strategy to obtain both passive and active targeting is the vectorization with a covalent bond between F127 and Biotin (a vitamin). Cancer cells can overexpress Biotin receptors, such as Avidin. Here, we evaluate the cytotoxic effects of the erythrosine-decyl ester (ERYDEC). This is a photosensitizer that can be utilized in photodynamic therapy (PDT) and incorporated in DPPC liposomes coated with F127 (F127/DPPC) and the biotinylated-F127 (F127-B/DPPC). The results showed that DPPC liposomes were efficiently mixed with common F127 or F127B, exhibiting adequate physical properties with simple and low-cost preparation. An HABA/Avidin assay showed the amount of Biotin available at the liposome surface. In addition, ERYDEC interaction with lipid vesicles showed high encapsulating efficiency and slow release kinetics. The ERYDEC monomeric species are represented by high light absorption and high singlet oxygen generation (1O₂), which confirm the presence of the drug in its monomeric state, as required for PDT. The ERYDEC/liposome system showed high stability and absence of significant cytotoxic effects (absence of light) in fibroblasts of the Mus musculus cell line. In addition, phototoxicity studies showed that ERYDEC/liposomes were able to inhibit cancer cells. However, in the biotinylated system, the effect was much greater than the common F127 coating. This dramatically decreased the inhibitory concentration of CC₅₀ and CC₉₀. In addition, cellular uptake studies based on fluorescence properties of ERYDEC showed that a two-hour incubation period was enough for the uptake by the cell. Therefore, the new vectorized-coated liposome is a potential system for use in cancer treatments, considering that it is a theranostic platform.

Keywords: Active targeting; Biotin; Coated liposomes; Drug delivery; Photodynamic therapy; Xanthene dye.