Design of fluorinated stealth poly(ε-caprolactone) nanocarriers

The covalent functionalization of polymers with fluorinated moieties represents a promising strategy for the development of multimodal systems. Moreover, polymer fluorination often endows the resulting nanocarriers with improved colloidal stability in the biological environment. In this work, we developed fluorinated pegylated (PEG) biodegradable poly(ε-caprolactone) (PCL) drug nanocarriers showing both high colloidal stability and stealth properties, as well as being (¹⁹F)-Nuclear Magnetic Resonance (NMR) detectable. The optimized nanocarriers were obtained mixing a PEG-PCL block copolymer with a nonafluoro-functionalized PCL polymer. The role of PEGylation and fluorination on self-assembly and colloidal behavior of the obtained nanoparticles (NPs) was investigated, as well as their respective role on stealth properties and colloidal stability. To prove the feasibility of the developed NPs as potential ¹⁹F NMR detectable drug delivery systems, a hydrophobic drug was successfully encapsulated, and the maintenance of the relevant ¹⁹F NMR properties evaluated. Drug-loaded fluorinated NPs still retained a sharp and intense ¹⁹F NMR signal and good relaxivity parameters (i.e., T₁ and T₂ relaxation times) in water, which were not impaired by drug encapsulation.