Controlled Microfluidic Synthesis of Biological Stimuli-Responsive Polymer Nanoparticles

摘要

Microfluidic flow-directed self-assembly of biological stimuli-responsive block copolymers is demonstrated with dual-location cleavable linkages at the junction between hydrophilic and hydrophobic blocks and on pendant group within the hydrophobic blocks. On-chip self-assembly within a two-phase microfluidic reactor forms various "DualM" polymer nanoparticles (PNPs), including cylinders and multicompartment vesicles, with sizes and morphologies that are tunable with manufacturing flow rate. Complex kinetically trapped intermediates between shear-dependent states provide the most detailed mechanism to date of microfluidic PNP formation in the presence of flow-variable high shear. Glutathione (GSH)-triggered changes in PNP size and internal structure depend strongly on the initial flow-directed size and internal structure. Upon incubation in GSH, flow-directed PNPs with smaller average sizes showed a faster hydrodynamic size increase (attributed to junction cleavage) and those with higher excess Gibbs free energy showed faster inner compartment growth (attributed to pendant cleavage). These results demonstrate that the combination of chemical control of the location of biologically responsive linkages with microfluidic shear processing offers promising routes for tunable "smart" polymeric nanomedicines.