Functionalized Mesoporous Silica Nanoparticle-Based Drug Delivery System to Rescue Acrolein-Mediated Cell Death

Abstract

Mesoporous silica nanoparticles (MSNs) were prepared and characterized to develop a drug delivery system by loading them with hydralazine and functionalizing them with polyethylene glycol. These agents restore damaged cell membranes and ameliorate abnormal mitochondria behavior induced by the endogenous toxin acrolein. Such a formulation shows potential as a novel therapeutic agent. MSNs with encapsulated hydralazine and covalently linked with polyethylene glycol were subsequently synthesized and characterized by transmission-electron microscopy, N(2) adsorption/desorption, x-ray diffraction and UV-vis spectroscopy. MSNs exhibited large surface area, pore volume and tunable pore size. The mean particle size was 100 nm and hydralazine encapsulation efficiency was almost 25%. These were tested using PC12 in culture to restore their disrupted cell membrane and to improve mitochondria function associated with oxidative stress after exposure to acrolein. Lactate dehydrogenase, MTT, ATP and glutathione assays were used to examine the physiological functioning of the samples and the loss of lactate dehydrogenase from the cytoplasm assayed the integrity of the membranes. These evaluations are sufficient to initially demonstrate drug delivery (concentrated hydralazine) into the compromised cells cytoplasm using the MSNs as a vehicle. MSNs modified with drug/polymer constructs provide significant neuroprotection to cells damaged by a usually lethal exposure to acrolein.