Replenishing Cation‑π Interactions for the Fabrication of Mesoporous Levodopa Nanoformulations for Parkinson Remission

Directly assembling drugs into mesoporous nanoformulations will be greatly favored due to the combination of enhanced drug delivery efficiency and mesostructure-enabled nanobio interactions. However, such an approach is hindered due to the lack of understanding of polymer nanoparticles’ formation mechanism, especially the relationship between polymerization, self-assembly, and the nucleation process. Here, by investigating the levodopa and dopamine polymerization process, we identify π-cation interaction as pivotal in the self-assembly and nucleation control of dopa molecules. Thus, through manipulation of the π-cation interaction, we present the direct assembly of a commercial drug, levodopa, into mesoporous nanoformulations. The synthesized nanospheres, approximately 200 nm in diameter, exhibit uniform mesopores of around 8 nm. These nanoformulations, abundant in mesopores, enhance chiral phenylalanine interaction with α-synuclein (Syn), curbing aggregation, safeguarding neurons, and alleviating Parkinson’s pathology. When combating α-synuclein, the nanoformulation achieved ∼100% inhibition of protein aggregation and sustained neuron viability up to 300%. We believe that this study may advance mesoscale self-assembly knowledge, guiding future nanopharmaceutical developments.