pH-Responsive polyelectrolyte coated gadolinium oxide-doped mesoporous silica nanoparticles (Gd2O3@MSNs) for synergistic drug delivery and magnetic resonance imaging enhancement.

Theranostic platforms that combine therapeutic and imaging modalities have received increasing interest. The development of theranostic nanovectors that can release therapeutic agents at pathological tissues in an on-demand manner and provide instantaneous feedback through non-invasive imaging techniques is of urgent need. Herein, a new magnetic resonance imaging (MRI) contrast agent, gadolinium oxide (Gd2O3), and an anticancer drug, doxorubicin (DOX), were co-loaded into mesoporous silica nanoparticles (MSNs) with the formation of hybrid Gd2O3@MSN-DOX nanoparticles. The hybrid nanoparticles were further coated with pH-responsive polyelectrolytes that underwent a charge reversal process at acidic pH. Upon entering into cells by folic acid (FA) receptor-mediated endocytosis, the mildly acidic pH within endolysosomes triggered the disassociation of the absorbed polyelectrolytes on the surfaces of the Gd2O3@MSN-DOX nanoparticles and thus actuated the DOX release, thereby exerting an anti-cancer effect. More importantly, the confinement of paramagnetic Gd2O3 within MSNs led to a remarkable increase of MRI relaxivity (r1 = 9.14 mM-1 s-1vs. 3.68 mM-1 s-1 of the clinically applied MRI contrast agent), likely due to the increased tumbling time and coordination number of water molecules. This work provides a feasible strategy to fabricate theranostic nanovectors with controlled release behavior triggered by mildly acidic pH and high-performance MR imaging capability.