Temperature-Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Apolipoproteins confer a 'stealth effect' to nanoparticles, reducing immune cell uptake and prolonging circulation time.
• Controlling apolipoprotein binding is crucial for optimizing nanocarrier stealth properties and drug delivery efficacy.

Purpose of the Study:

• To present a novel strategy for specific apolipoprotein binding to nanoparticles by temperature modulation.
• To investigate the influence of temperature-dependent protein corona formation on nanoparticle stealth behavior and cellular uptake.

Main Methods:

• Preparation of nanoparticles with a temperature-responsive poly(N-isopropylacrylamide) shell.
• Incubation of nanoparticles in human plasma at different temperatures (25°C and 37°C).
• Label-free quantitative liquid chromatography-mass spectrometry to identify bound apolipoproteins.
• Assessment of nanoparticle uptake by RAW264.7 and HeLa cells.

Main Results:

• Nanoparticles showed temperature-dependent apolipoprotein enrichment: apolipoprotein J (clusterin) at 25°C and apolipoprotein A1/E at 37°C.
• The specific protein corona composition significantly altered nanoparticle uptake by immune and non-immune cells.
• Demonstrated control over nanoparticle stealth behavior through temperature-responsive functionalization.

Conclusions:

• Temperature-responsive materials enable tunable apolipoprotein binding on nanoparticles.
• This approach offers a promising strategy for engineering nanocarriers with controlled stealth properties for enhanced drug delivery.
• The findings highlight the potential of surface chemistry modulation for optimizing nanomedicine performance.