Electrically pulsatile responsive drug delivery platform for treatment of Alzheimer's disease

Metal ions are involved in Aβ aggregate deposition and neurotoxicity via various processes, including acceleration of Aβ aggregation, disruption of normal metal homeostasis, and formation of reactive oxygen species (ROS). Although metal chelation is a promising therapeutic strategy for Alzheimer's disease (AD), the widespread use of chelation therapy faces a significant problem; namely, it is difficult to differentiate toxic metals associated with Aβ plaques from those required by normal metal homeostasis. Furthermore, the multifactorial nature of AD and the current lack of an accepted unitary theory to account for AD neurodegeneration also restrict AD treatment through a single therapeutic strategy. This paper presents a novel bifunctional platform by integrating nonpharmacological and pharmacological cues into one system for AD treatment. This electrically responsive drug release platform, based on conducting polymer polypyrrole (PPy) incorporated with graphene-mesoporous silica nanohybrids (GSN) nanoreserviors, could realize on-demand controlled drug delivery with spatial and temporal control. Electrochemical stimulation can treat peripheral nerve injury (PNI) to stimulate neurite outgrowth. This novel system can also effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ-related toxicity. The purpose of this research is to promote the design of noninvasive remote-controlled multifunctional systems for AD treatment.