Polydopamine Coatings in Confined Nanopore Space: Toward Improved Retention and Release of Hydrophilic Cargo

A composite nanocarrier system integrating the porous structure of mesoporous silica nanoparticles (MSNs) and the adhesive property of polydopamine (PDA) for loading and release of hydrophilic drugs is reported. Amino group functionalization facilitates the oxidant-induced surface polymerization of dopamine in the confined space of mesopores by Schiff base/Michael addition reaction in a mild synthesis. As a consequence, MSN@PDA particles have an average pore size of 4.0 nm, a particle diameter of ∼70 nm, as well as a thin layer of polydopamine coating on the surfaces of MSNs. The MSN@PDA nanocarriers can effectively adsorb hydrophilic drugs with high loading capacities (380 μg/mg for doxorubicin hydrochloride (DOX) and 320 μg/mg for calcein), facilitated by the π–π stacking interactions between the abundant aromatic rings of PDA and the aromatic backbones of drugs. Interestingly, sustained and pH-dependent drug release was observed for these drug-loaded MSN@PDA particles, owing to the adhesive property of polydopamine like “molecular glue”. Moreover, a catechol–metal–drug coordination system can be easily constructed on the basis of the coordination bonding between catechols in polydopamine and transition metal ions (Fe³⁺, Zn²⁺) as well as that between metal ions and anthracycline drugs (i.e., DOX), resulting in an acid-triggered drug release