Novel pore-expanded mesoporous silica nanoparticles (MSNs) with pore sizes of approximately 11nm were synthesized and modified with thermoresponsive, poly(n-isopropylacrylamide) (PNIPAM) gating groups on the nanoparticle exterior surface and in addition with poly(ethylene-glycol) (PEG) within the porous interior to minimize protein adsorption. PEG traditionally has been grafted to the nanoparticle exterior to minimize non-specific binding and interactions with the biological environment, but due to the templating mechanism of MSN synthesis, both the pore interior and nanoparticle surface can be separately modified. Here, an improved control release behavior of bovine hemoglobin (BHb) was observed after PEGylating the interior porous framework, compared to the release BHb from unmodified MSNs. This can be attributed to the reduced protein denaturation on PEGylated silica that was observed using circular dichroism spectroscopy.