Biocompatible Soft Nanoparticles with Multiple Morphologies Obtained from Nanoprecipitation of Amphiphilic Graft Copolymers in a Backbone-Selective Solvent

Stealth nanocarriers are a promising technology for the treatment of diseases. However, the preparation and characterization of well-defined soft nanoparticulate systems remain challenging. Here we describe a platform of amphiphilic graft copolymers leading to nanoparticles with multiple morphologies and the role of the hydrophilic backbone in their interaction with a model protein. The amphiphilic graft copolymers platform was composed of hydrophilic backbone poly(2methyl-2-oxazoline-co-2-pentyl-2-oxazoline) (P(MeOx-co-PentOx)), prepared via cationic ring-opening polymerization. Hydrophobic poly(pp lactide) (PLA) chains were grafted on the backbone via Huisgen 1,3 dipolar cycloaddition. The click copper-catalyzed cycloaddition reactions of azides with alkynes (CuAAC) were successfully carried out, and a series of amphiphilic copolymers were prepared containing a backbone with a number-average molecular weight of 14.2 X 10(3) g mol(-1) and different hydrophobic PLA grafts with various molecular weights (2.8 X 10(3)-12.4 X 10(3) g mol(-1)). These original architectures of copolymers, when nanoprecipitated in water, the backbone-selective solvent, allowed us to obtain various structures of nanoparticles with a hydrodynamic diameter in the, range of 65-99 nm. More interestingly, a plurality of morphologies going from unilamellar, multilamellar, and large compound vesicles to core shell nanopartides and depending on the PLA molecular weights were evidenced by combining cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS) studies. A first evaluation of their stealthiness by studying the stability and the interaction of these nano-objects with a model protein revealed the role played by the P(MeOx-co-PentOx) in these interactions, demonstrating the utility of this amphiphilic graft copolymers platform with well-defined architectures for the design of nanocarriers in drug'delivery applications.