Dual-Stimuli Responsive Cystamine-Modified Polydopamine Coatings as Payload Gatekeepers

We present cystamine-modified polydopamine (PDA) coatings as tunable gatekeepers for mesoporous silica nanoparticles (MSNs) in drug delivery. Unlike conventional post-functionalization strategies, cystamine moieties were incorporated directly into the PDA network, enabling tunable shell composition and redox responsiveness by simply adjusting the dopamine-to-cystamine ratio. By varying the cystamine:dopamine ratio, pH- and redox-responsive release of doxorubicin (DOX) and sorafenib (SO) was achieved, with release kinetics following the Higuchi model. Cystamine-modified PDA nanoparticles with varying disulfide bridge content were synthesized and comprehensively characterized using SEM, TGA, FTIR, and zeta potential measurements. The cystamine content was found to influence thermal stability, coating performance, and protective properties. Importantly, increasing disulfide content did not necessarily improve release performance, suggesting that excessive crosslinking may partially restrict shell permeabilization and drug diffusion. These findings reveal important structure-property relationships in catechol-based coatings and underline the significance of disulfide linkages in the design of bioinspired stimuli-responsive drug delivery systems.