Biological camouflage imparts cell-like activity to injectable particles: the leukolike delivery system

The objective of this thesis is to demonstrate that increased localization of theranostic particles at the tumor site can be achieved by developing a novel biomimetic hybrid DDS capable of simultaneously escaping biobarriers, while targeting the cancerous lesion. In order to improve the stealth properties of the drug delivery system (DDS) an innovative liposome formulation composed of natural phospholipids obtained through the extraction of the cellular membranes of leukocytes isolated from the peripheral blood has been proposed. This new generation of liposomes composed of the same lipids and proteins of the blood circulating leukocytes are biologically inert and weakly immunogenic. Moreover the presence of some membrane proteins can transfer to the liposomes their biological functions thus improving the liposome targeting ability without requiring following surface functionalization. The leukocyte-derived liposomes can be used as coating material for the realization of biomimetic DDS called “leukolike” system (LS), since it combine the natural properties of leukocyte cells (free circulation in the blood stream, transendothelial migration and tropism towards the inflammatory site) with the characteristics of an artificial delivery system (biodegradability, biocompatibility, agents loading and release). The LS thus demonstrates the advantages of a novel delivery strategy able to bestow a DDS with prolonged circulation, selective tumor targeting and enhanced tumor accumulation and retention.