Liposome interactions with biological systems: a journey into cells

Nanomedicine has been rapidly developed in the last decades. However, the clinical translation of nano-formulations remain challenging and relatively few nanomedicines have been approved for clinical use. One of the main obstacles in the development of nanomedicines is the still limited understanding of nanomaterial interactions with biological systems.

In this context, using liposomes, one of the most clinically established nano-formulations, as a nanomedicine model, this Thesis studied nanocarrier behavior in complex biological systems, in order to explore new strategies to guide the design of more effective nano-formulations. Liposome composition was changed systematically in order to obtain formulations with different biological outcomes. This allowed to gain a better understanding on how nanomaterial design can be tuned to control the protein corona forming on their surface once introduced in serum, modulate cell uptake efficiency and kinetics, affect the mechanisms cells used for their internalization and the kinetics of drug release following uptake by cells. Additionally, biomimetic nanotechnology, an alternative strategy to fabricate nanoparticles with defined interactions with biological systems, was exploited to dope liposomes with cell membranes from stromal and leukemia cells in the context of acute myeloid leukemia (AML). Our results suggested that stromal cell membrane-doped liposomes had the potential to be developed as a tool to characterize the interactions between stromal and leukemia cells and to identify novel targets for AML treatment.

The results presented in this Thesis have helped to deepen our knowledge on how complex biological systems affect nanomaterial behavior.