Cell Membrane Biomimetic Nanoparticles with Potential in Treatment of Alzheimer’s Disease



1. Introduction

2. BBB Hinders AD Treatment

2.1. Current Therapy Strategy

2.2. The Impact of BBB on Treatment of AD

2.3. New Strategies for Treating AD through BBB

2.3.1. Route of Administration for Treating AD

2.3.2. Potential Agents for AD Treatment

2.3.3. Nanoparticle Technology for Treating AD

3. Core NPs

3.1. NPs

3.1.1. Polymeric NPs

3.1.2. Lipid-Based NPs

3.1.3. Inorganic NPs

3.2. Synthesis of Core NPs

3.2.1. Single Emulsification–Solvent Evaporation Method

3.2.2. Double Emulsion Method

3.2.3. Nanoprecipitation Method

3.2.4. Salting out Emulsification–Diffusion Method

3.2.5. Supercritical Fluid Method

3.2.6. Spray Drying Method

3.2.7. Solvothermal Method

3.2.8. Sol–Gel Method

3.2.9. Thermal Decomposition

4. Cell Membrane

4.1. Source Cell

4.1.1. Erythrocyte

4.1.2. Platelet

4.1.3. Leukocyte

4.1.4. Macrophages

4.1.5. Cancer Cells

4.1.6. Membrane Hybridization

4.1.7. Other Cells

4.2. Isolation of Cell Membrane

4.2.1. Ultrasound

4.2.2. Freeze–Thaw

4.2.3. Extrusion

4.2.4. Hypotonicity

4.2.5. Dounce Homogenizer

4.3. Fusion of Membrane Vesicles and NPs

4.3.1. Co-Extrusion

4.3.2. Ultrasound

4.3.3. Microfluidic Electroporation

4.3.4. Other Coating Methods

5. Targeting Peptides

6. Concluding Remarks and Future Perspectives

Author Contributions


Institutional Review Board Statement

Informed Consent Statement

Data Availability Statement

Conflicts of Interest


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Cell Separation Methods Properties Limitations
Erythrocyte Extrusion, ultrasound, freeze–thaw, and hypotonicity Easy availability. Poor targeting ability.
Long circulatory lifespan (~120 days in humans and ~50 days in mice) and wide circulation range.
Uniform in size and shape, with a good surface area to volume ratio, without organelles and any DNA.
Good biocompatibility, biodegradability, and non-immunogenicity.
Platelet Extrusion, freeze–thaw, and ultrasound High targeting efficiency. Small proportion of blood and undesirable activated.
Controlled drug release.
Lower immunogenicity.
Long systemic circulation (around 7–10 days).
Targeting to plaque.
Leukocyte Extrusion and hypotonicity Adhesion capacity. Organization residency restrictions.
Migratory and chemotactic capacity in disease states.
High loading capacity.
Macrophage Extrusion and hypotonicity Good targeting ability to AD lesions. Organization residency restrictions.
Innate immune evasion ability.
Long circulation ability in vivo.
Cancer cell Extrusion and Dounce homogenizer Strong homologous targeting ability. Homologous tumor targeting.
Method Procedures Advantages Disadvantages
Co-extrusion The mixed solution formed by mixing the cell membrane suspension and the NPs suspension is co-extruded through a porous filter membrane of specified size with an extruder for many times The steps are simple and easy to use. Time-consuming and labor-intensive.

Low synthesis rate

The multi-layer target product can be prepared
Ultrasound The mixture formed by mixing the cell membrane suspension and the NPs suspension is sonicated at a certain frequency for a specified time Less loss of raw materials; mass production is possible. Uneven coating, easy to form polydisperse particles.

NPs are easily broken

The biomimetic NPs formed are highly stable.
Membrane hybrids can be formed
Microfluidic electroporation The cell membrane suspension and NPs suspension are mixed separately in the instrument, flow through the electroporation area, and finally the product is collected in the chip High synthesis rate and good parallelism Complex operation process
Target Receptor or Transport Pathway Name Peptide Sequence Ref.
Low-density lipoprotein receptor Angiopep-2 TFFYGGSRGKRNFKTEEY [130]
Peptide-22 Ac-CMPRLRGC-NH2 [134]
Transferrin receptor B6 CGHKAKGPRK [135]
D-T7 d-HRPYIAH [136]
T7 HAIYPRH [136]
THRre pwvpswmpprht-NH2 [138]
Nicotinic acetylcholine receptor RVG29 YTIWMPENPRPGTPCDIFTNSRGKRASNG-OH [57]
DCDX GreirtGraerwsekf-OH [116]
Potassium or calcium channel Apamin CNCKAPETALCARRCQQH-NH2 [142]
MiniAp-4 H-[Dap]KAPETAL D-NH2 [135]
Glutathione transporter GSH γ-l-glutamyl-CG-OH [143]
Adsorption-mediated endocytosis TAT(47-57) YGRKKRRQRRR-NH2 [145]
Unknown receptor CGN d-GNHPLAKYNGT [136]
Aβ aggregates LVFFA LVFFA [149]
Sphingomyelin and ganglioside GT1B on neurons Tet1 HLNILSTLWKYR [151]

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Zhong, X.; Na, Y.; Yin, S.; Yan, C.; Gu, J.; Zhang, N.; Geng, F. Cell Membrane Biomimetic Nanoparticles with Potential in Treatment of Alzheimer’s Disease. Molecules 2023, 28, 2336. https://doi.org/10.3390/molecules28052336

Zhong X, Na Y, Yin S, Yan C, Gu J, Zhang N, Geng F. Cell Membrane Biomimetic Nanoparticles with Potential in Treatment of Alzheimer’s Disease. Molecules. 2023; 28(5):2336. https://doi.org/10.3390/molecules28052336

Chicago/Turabian Style

Zhong, Xinyu, Yue Na, Shun Yin, Chang Yan, Jinlian Gu, Ning Zhang, and Fang Geng. 2023. “Cell Membrane Biomimetic Nanoparticles with Potential in Treatment of Alzheimer’s Disease” Molecules 28, no. 5: 2336. https://doi.org/10.3390/molecules28052336

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