Development of biodegradable nanoparticles for targeting Tumor Associated Macrophages: synthesis, investigation of the role of the surfactant and surface decoration in complex media

Tumor Associated Macrophages (TAMs) are involved in cancer proliferation, thus strategies to deplete them represent promising tools for chemotherapy. Pharmacological agents with multiple activities such as curcumin and RNA interference have been proposed; however their employment in therapeutics has been limited because of low systemic bioavailability. Accordingly, this thesis described as an innovative therapeutic approach for cancer treatment the development of polymeric nanoparticles (NPs) able to (i) increase pharmacokinetics properties of biomacromolecules and poor water soluble drugs, and (ii) guarantee TAMs specific targeting. The safe and versatile polymer Poly(Lactic-co-Glycolic)Acid (PLGA) has been used for the synthesis of NPs by both single (OW) and double (WOW) emulsion-solvent evaporation techniques. Different synthetic parameters have been taken into consideration, with particular focus on the surfactant role. As alternative to the commonly used Poly Vinyl Alcohol (PVA), a newly synthetized polymer (amino-PVA) and Calcium Sterate (CSt) have been investigated for their ability to modulate surface charge and biocompatibility. NPs with solid or core-shell structures, whose size was tailored between 200 and 300 nm, were obtained and a thorough characterization has been performed, with the help of innovative techniques such as single particle optical extinction and scattering (SPES) method. Both amino-PVA and CSt stabilized NPs were found to be able to load curcumin and biomacromolecules, either alone or in combination. Strategies for surface decoration with the employment of D-mannose as specific molecule to guarantee TAMs recognition were proposed. Finally, cytocompatibility of the amino-PVA and CSt stabilized NPs have been assessed.