Smart Nanocarrier Based on Poly(oligo(ethylene glycol) methyl ether acrylate) Terminated pH-Responsive Polymer Brushes Grafted Mesoporous Silica Nanoparticles

Abstract

A platform technology based on inorganic/organic nanoparticles for carrying drugs could be of enormous potential benefit in treating cancer. Surface modification of the nanoparticles with pH-responsive and biocompatible polymers can improve the selectivity and targeting toward the tumor cells. Polyethylene glycol (PEG) and its derivatives being present on the surface could enhance the ability to tailor nanomaterial hydrophilicity and to resist the adhesion of proteins and/or cells. Herein, we report a new nanoplatform based on mesoporous silica nanoparticles (MSNs) conjugated with poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) brushes as a candidate for stimuli-responsive intracellular drug delivery system. Alkyl bromide functional initiators (end-functionalized PDEAEMA brushes) were derivatized to amine, followed by the reaction with ethylene sulfide and poly(oligo(ethylene glycol) methyl ether acrylate (POEGMEA). Using X-ray photoelectron spectroscopy (XPS) to examine the attachment of POEGMEA, it was found that the POEGMEA molecules in the outer surface of PDEAEMA brushes have been successfully reacted with thiol groups, as indicated by the increase in the peak intensity of the C–O group at 286.5 eV. Brush-modified silica hybrids have an average diameter of ca. 250 nm, as estimated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Rhodamine B dye was loaded into the brush-modified silica hybrids nanoparticles with loading capacity of ca. 74%. The accumulated dye released from brush-modified particles in acidic media was approximately 60%, whereas the dye amount release in basic media was less than 15% after 10 h exposure time. Alamar Blue assay was used to assess the cytotoxicity of MSNs–PDEAEMA, MSNs–PDEAEMA–SH, and MSNs–PDEAEMA–POEGMEA. The results show that all three nanosystems were non-toxic to hMSC with an increase in cell proliferation for MSNs–PDEAEMA–POEGMEA at 50 µg/mL after both 24 and 48 h of incubation.