RVG-functionalized microglial membrane-coated cerium-gallic acid metal-organic frameworks for multi-target...

Area of Science:

• Nanomedicine
• Neuroscience
• Materials Science

Background:

• Alzheimer's disease (AD) pathology involves complex factors like amyloid-beta (Aβ) aggregation, oxidative stress, neuroinflammation, and metal ion imbalance.
• Conventional single-target therapies for AD have limited efficacy due to the multifactorial nature of the disease.

Purpose of the Study:

• To develop a multifunctional nanotherapeutic platform for synergistic Alzheimer's disease (AD) treatment.
• To engineer a biomimetic nanosystem (CeGA-MOF/B/R) for enhanced brain delivery and multi-target therapeutic action.

Main Methods:

• Fabrication of a cerium-gallic acid bio-metal-organic framework (CeGA-MOF) with inherent ROS scavenging and metal chelating properties.
• Coating CeGA-MOF with microglial membranes and functionalizing with rabies virus glycoprotein (RVG) peptide to create a biomimetic nanosystem (CeGA-MOF/B/R).
• In vitro evaluation of metal ion chelation, Aβ aggregation inhibition, and neuroprotection; in vivo assessment in APP/PS1 transgenic mice.

Main Results:

• CeGA-MOF/B/R effectively chelated key metal ions (Cu2+, Zn2+, Fe3+), inhibited metal-induced Aβ aggregation, and protected neurons in vitro.
• The nanosystem demonstrated improved in vivo stability and blood-brain barrier penetration.
• In APP/PS1 mice, CeGA-MOF/B/R reduced cerebral Aβ burden, promoted anti-inflammatory microglial polarization, and improved cognitive function.

Conclusions:

• The developed biomimetic nanoplatform (CeGA-MOF/B/R) offers a promising multi-target strategy for Alzheimer's disease therapy.
• This approach synergistically addresses key pathological hallmarks of AD, including oxidative stress, Aβ aggregation, and neuroinflammation.
• The engineered nanosystem holds potential for enhanced brain delivery and therapeutic efficacy in AD treatment.