Micellar nanosystems based on functionalized amphiphilic copolymers of N-vinylpyrrolidone for creating theranostic platforms

Polymeric drug delivery systems attract increased attention due to their ability to ensure accurate delivery of active substances exact to the site of action as well as reduce off-target cytotoxicity, which is extremely important during the chemotherapy of cancer. Amphiphilic copolymers of N-vinylpyrrolidone containing a terminal hydrophobic moiety are capable of forming micellar structures with hydrophobic core and hydrophilic corona in an aqueous medium, where a hydrophobic drug can be encapsulated in the micelles core. In this work, the PVP copolymers containing one terminal thiooctadecyl group were functionalized with acrylic acid. The presence of free carboxylic acid groups in the hydrophilic micellar shell provides ample opportunities for modifying the surface of micelles to create theranostic platforms.
Copolymers of acrylic acid and N-vinylpyrrolidone containing only one terminal hydrophobic group were obtained in the molecular weight range from 3.5 to 11 kDa. The synthesis was carried out in dioxane solution for 3 hours at a temperature of 70oC in the presence of dinitrile azobisisobutyric acid as radical polymerization initiator and octadecyl mercaptan (C18H37SH) as chain transfer agent.
The structure of the copolymers was confirmed by 13C and 1H NMR spectroscopy and MALDI-TOF mass spectrometry. Nanoaggregates of copolymers were obtained by ultrasonic dispersion. The average hydrodynamic diameter of the particles and the particle size distribution (polydispersity index, PDI) were determined by dynamic laser light scattering (DLS). The determination of the surface charge of the particles (zeta potential) was carried out by microelectrophoresis on the Zetasizer Nano ZS analyzer (Malvern Instruments, Great Britain). The nanoparticles had sizes ranging from 30 to 200 nm and a weakly negative surface charge from -21 to -14 mV.
The obtained micelles can be functionalized with gadolinium as a contrast agent for MRI. Furthermore, the presence of free groups of carboxylic acids allows us to covalently attach fragments aimed at cancer cells to the polymer (FALGEA peptide). Thus, the unique structure of the obtained nanoscale micelles can ensure the delivery of an active substance encapsulated in the micelle core simultaneously with a selectivity agent and/or an imaging agent immobilized on the micellar corona, which open up broad prospects for the diagnosis and therapy of cancer diseases.