Abstrakt
Diverse macromolecular delivery systems have been created to increase the stability and potency of peptide vaccines. However, many of them are insufficient in size and morphology to ensure efficient interaction between immunogens and immune cell receptors.
Moreover, they are often released too slowly from the body after performing their desired function. To overcome these limitations, we have developed novel biocompatible polymer-colloidal carriers based on maghemite (gamma-Fe2O3) nanoparticles coated with poly[N-(2-hydroxypropyl) methacrylamide] (p(HPMA)) polymers.
Various types of p(HPMA) polymers (semitelechelic homopolymers, statistical copolymers and di-block copolymers) are attached to the surface of the gamma-Fe2O3 particles via an iron-chelating deferoxamine group linked to the ends of their chains through stable or stimuli-responsive bonds. The resulting nanoparticles are stable and well-defined with negligible toxicity and of a suitable hydrodynamic size.
They also feature a high number of binding sites for attaching peptide immunogens. Nanoparticles with polymers attached via reducible disulphide bonds exhibited rapid decoating upon incubation in the solutions, mimicking a reductive intracellular environment.
In addition, we successfully conjugated a minimal peptide immunogen (V3) derived from the HIV-1 binding site to representative polymer-colloidal systems, demonstrating their suitability for vaccine delivery. Finally, the superparamagnetic properties of these nanoparticle vaccines enable their detection by MRI, which can be used to monitor biodistribution and pharmacokinetics.