Conventional polyelectrolytes are known to form complexes with counterparts of the opposite charge and with some ampholytic macromolecules, such as proteins. However, few of these complexes display sufficient stability under physiological conditions in order to be considered for biomedical applications, especially for the delivery of biopharmaceuticals. Even fewer of them can degrade into physiologically benign products - a prerequisite for use as injectables. Water-soluble ionic polyphosphazenes appear to successfully meet these requirements. Since the discovery of potent immunostimulating properties of poly[di(carboxylatophenoxy)phosphazene], PCPP and its structural derivatives, mechanistic aspects of their activity have drawn significant attention. Today, the accumulated physico-chemical and biophysical data reveal that polyphosphazenes are capable of spontaneous self-assembly with antigenic proteins in aqueous solutions. The resulting physiologically stable supramolecular complexes mimic viruses in terms of dimensions, effective presentation of antigens to immunocompetent cells, and display of the appropriate ‘danger signals’, such as Toll-Like Receptor (TLR) agonists. The composition and macromolecular architecture of polyphosphazene ‘module’ of the supramolecular assembly serves as a determinant for enhanced recognition by the host immune system or its evasion, efficiency of cellular uptake or intracellular pathway of the protein cargo, physiological persistence and shelf-life of the complex. The self-assembly feature of ionic polyphosphazenes coupled with the appropriate modulation of their structures has been now extended to the delivery of small-molecule drugs, such as anticancer therapies, immunomodulators, and antibacterial agents. Furthermore, a growing family of self-assembling ionic fluoropolyphosphazenes, which introduces a unique set of lipophobic and hydrophobic (omniphobic) properties into all-aqueous biopharmaceuticals and nano-structured materials, starts to play an increasingly intriguing role in advancing molecular engineering of biomaterials and drug delivery constructs.

Multifunctional polyphosphazenes and their nano-assembly in aqueous solutions - from virus mimicking constructs to engineered biomaterials

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.