Mesoporous Silica Nanoparticle‐based H₂O₂ Responsive Controlled‐Release System Used for Alzheimer's Disease Treatment

Abstract

Metal ions play important roles in amyloid aggregation and neurotoxicity. Metal-ion chelation therapy has been used in clinical trials for Alzheimer's disease (AD) treatment. However, clinical trial studies have shown that long-term use of metal chelator can cause adverse side effect, subacute myelo-optic neuropathy. Nanoparticle engineering processes have become promising approaches for efficiently drugs delivery. A series of modified mesoporous silica nanoparticles (MSNs) using redox, pH, competitive binding, light, and enzyme as actuators have been demonstrated. Recently, significant advances in sensing oxidative stress have been made by taking advantage of specific chemistry between cellular oxidants such as H(2) O(2) . Here we report a biocompatible delivery platform by using H(2) O(2) responsive controlled-release system to realize target delivery of AD therapeutic metal chelator. The advantage of this novel strategy is that metal chelator can only be released by the increased levels of H(2) O(2) , thus, it would not interfere with the healthy metal homeostasis and can overcome strong side effect of metal chelator after long-term use. By taking advantage of the good biocompatibility, cellular uptake properties, and efficient intracellular release of metal chelators, the delivery system is promising for future in vivo controlled-release biomedical applications.

Apoptosis in Alzheimer’s Disease: An Understanding of the Physiology, Pathology and Therapeutic Avenues

“…Further, anti-Ab monoclonal antibodies Bapineuzumab, Solanezumab also failed to show neuroprotective effect in phase III clinical trials of AD in turn inducing side effects such as meningoencephalitis, vasogenic edema in patients [118]. Mesoporous silica nanoparticles which selectively release the cargo in response to the augmented levels of H 2 O 2 substantially circumvents strong side effect of long term metal chelator use without affecting healthy metal homeostasis [119]. A robust nanocarrier that can span the blood brain barrier and can encapsulate and release several types of drugs to the brain may substantially reverse the AD symptoms.…”

Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

“…Geng et al 119 reported a biocompatible and H 2 O 2 -responsive controlled-release system to realize target delivery of Alzheimer's disease therapeutic metal chelator. As illustrated in Figure 10, the system was consisted of a mesoporous nanoparticle functionalized with a derivative of aryl boronic acids by forming stable cyclic esters with the adjacent diols of saccharides.…”

Transition-metal-substituted polyoxometalate derivatives as functional anti-amyloid agents for Alzheimer’s disease

“…This order was consistent with our quantitative thermodynamics results. Recent evidence suggests that amyloid oligomers, which represent intermediates in the fibril formation process, are the main source of cytotoxicity by causing the death of neurons for amyloid pathogenesis, rather than the mature fibrils that accumulate as large aggregates 41,42 . To verify the feasibility of the POMds for AD therapeutic applications, we studied their inhibitory effects on Ab oligomers.…”

“…The metal-induced oligomer of Ab was prepared by treatment with Cu 2 þ at 37°C for 24 h and determined by a native polyacrylamide gel electrophoresis (PAGE) assay ( Supplementary Fig. 10) 42 . Lane 2 in Supplementary Fig.…”