LAUSR

Self-assembled colloidal gels are highly versatile 3D nanocluster platforms with potential to overcome the rapid clearing issues associated with standard free nanotherapeutics administration. However, the development of nanoassembled colloidal gels exhibiting autonomous multi-particle release from the bulk particle network remains elusive. Herein, we generated multi-particle colloidal gels from two nanosized building blocks, cationic poly(D,L-lactide-co-glycolide)-polyethyleneimine (PLGA-PEI) nanoparticles and anionic Zein-hyaluronan (HA) nanogels that assemble into macrosized 3D constructs via attractive electrostatic forces. The resulting colloidal gels exhibited high stability in complex culture medium as well as fit-to-shape moldable properties and injectability. Moreover, nanoassembled colloidal gels encapsulated bioactive quercetin flavonoids with high loading efficacy and presented a remarkably anti-inflammatory activity, reducing key pro-inflammatory biomarkers in inflammation-activated macrophages. More importantly, due to their rationally selected building blocks Zein-HA/PLGA-PEI self-assembled colloidal platforms displayed autonomous multi-particle shedding. Both positive and negative particles released from the colloidal system were efficiently internalized by macrophages along time as evidenced by quantitative particle uptake analysis. Overall, the generated nanostructured gels represent an implantable versatile platform for focalized multi-particles delivery. In addition, the possibility to combine a higher number of particle species with different properties or stimuli-responsiveness enables the manufacturing of combinatorial nanostructured gels for numerous biomedical applications.