Poly(allylamine)-tripolyphosphate Ionic Assemblies as Nanocarriers: Friend or Foe?

APUZZO E; AGAZZI M; HERRERA S; PICCO A; RIZZO G; CHAVERO C; BIANCHI D; SMALDINI P; PADULA G; SEOANE A; ALOMAR ML; DENOFRIO MP; DOCENA G; AZZARONI O

ACS Applied Bio Materials

American Chemical Society

Año: 2023 vol. 6 p. 4714 - 4727

Designing effective drug nanocarriers that are easyto synthesize, robust, and nontoxic is a significant challenge innanomedicine. Polyamine-multivalent molecule nanocomplexesare promising drug carriers due to their simple and all-aqueousmanufacturing process. However, these systems can present issuesof colloidal instability over time and cellular toxicity due to thecationic polymer. In this study, we finely modulate the formationparameters of poly(allylamine-tripolyphosphate) complexes tojointly optimize the robustness and safety. Polyallylamine wasionically assembled with tripolyphosphate anions to form liquidlikenanocomplexes with a size of around 200 nm and a zetapotential of −30 mV. We found that nanocomplexes exhibittremendous long-term stability (9 months of storage) in colloidaldispersion and that they are suitable as protein-loading agents. Moreover, the formation of nanocomplexes induced bytripolyphosphate anions produces a switch-off in the toxicity of the system by altering the overall charge from positive to negative. Inaddition, we demonstrate that nanocomplexes can be internalized by bone-marrow-derived macrophage cells. Altogether, thesenanocomplexes have attractive and promising properties as delivery nanoplatforms for potential therapies based on the immunesystem activation.