# Hybrid Membrane‐Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease

## TL;DR

Scientists developed a new nanoparticle delivery system that crosses the blood-brain barrier to target and treat Alzheimer's disease by reducing inflammation and cognitive decline.

## Contribution

A hybrid cell membrane coating is designed to enhance targeting precision and enable multitarget drug delivery for Alzheimer's therapy.

## Key findings

- Hybrid membrane-coated nanoparticles successfully cross the blood-brain barrier and target neuroinflammatory lesions.
- Drug-loaded liposomes reduced amyloid plaque deposition and cognitive impairments in a mouse model of Alzheimer's disease.
- Combining two drugs with different mechanisms improved therapeutic outcomes in Alzheimer's treatment.

## Abstract

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single‐mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug‐loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane‐coated nanomaterials offer new opportunities for precise drug delivery and disease‐specific targeting, which represent a versatile platform for targeted therapy in AD.

A novel cell membrane coating is designed by hybridizing the membranes from platelets and chemokine receptor 2 overexpressing cells to cross the blood brain barrier (BBB) and target neuroinflammatory lesions. Rapamycin and 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU) are loaded into the liposomes to achieve a synergistic therapy. These drug‐loaded hybrid cell membrane‐coated liposomes precisely target specific lesions and ameliorate cognitive deficiency in Alzheimer's disease.