Despite their great potentials as biomacromolecues delivery vehicles, there are few, if any, reports on mesoporous silica nanoparticles (MSNs) simultaneously integrated with the merits of large pore size, small particle diameters and well-ordered mesostructure. Here, we designed a facile strategy for the synthesis of monodispersed MSNs using cationic surfactants (CSs) as templating agents, neutral amine of N,N-dimethylhexadecylamine (DMHA) as a pore size mediator and tri-block copolymer of F127 (EO106PO70EO106) as a particle growth inhibitor/dispersant. The obtained colloidal nanoparticles exhibited a highly ordered mesostructure and tunable pore diameter up to 4.6 nm (BJH) and monodispersed particle sizes less than 150 nm. A model protein of cytochrome c (CytC) was exemplified to be accommodated in the resultant MSNs and its loading amount was correlated with their pore size. The efficient cancer cellular uptake of the large-pore MSNs prefigured their potentials as intracellular delivery vehicles for membrane-impermeable proteins. (C) 2013 Elsevier Inc. All rights reserved.