TAILOR-MADE VINCRISTINE-LIPOSOME FOR TARGETING TUMOR CELLS

To deliver molecules with therapeutic potentials and overcome drawbacks such as poor solubility, toxicity or short half-life, nanomedicine are continuously engineered. They are carried to their cellular destination either passively or actively through distinctive assets of the cell membranes. Among such assets, differences in the physicochemical properties of the cell membrane between tumor and non-tumor cells, like membrane fluidity, have been reported, but have little been underexplored for drug delivery purposes. In this study, we developed a new approach to ensure selective targeting based on membrane fluidity and physico-chemical compatibility between the biological membrane of the target cell and the lipid membrane of the liposome carriers (Bompard et al. 2020 and Abawi and Wang et al. 2021)

To this end, lipid-based carriers with different membrane fluidities were designed and used to deliver vincristine, a potential anti-tumor molecule extracted from Madagascar’s periwinkle. Vincristine inhibits the polymerization of microtubules by disrupting mitotic spindle dynamics and thus blocking mitosis. This drug was encapsulated in liposomes of controlled membrane fluidity and the interaction of vincristine-loaded liposomes was analyzed on prostate, colon and breast cancers’ cell lines and compared with non-tumor controls.

Among the tested compounds, liposomes having a fluid membrane loaded with vincristine induced a significant decrease of cancers’ cell lines viability in contrast to the control line. The intracellular release of vincristine from the lipid carriers was highlighted by the disruption of mitosis specific labeling of the actin filaments of metastatic prostate cell line visualized with confocal microscopy.

Delivery of liposomes to tumors was further analyzed on, 3D printed tumor models to mimic in vivo situation. Good diffusion of liposomes in the cell-containing gel was observed, and specific interaction with tumor cells was achieved.

Altogether, tailor-made liposomes encapsulating vincristine, with an adapted membrane fluidity, may be an interesting example of drug carriers and permit one to achieve selective delivery both on 2D and 3D tumor models.