Rational Synthesis of Virus-Mimicking Nanocarriers for Enhanced Intracellular Delivery through Polyvalent...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Designing nanocarriers with controlled surface properties is crucial for effective cellular interaction and intracellular trafficking.
• Current methods face challenges in precisely manipulating nanocarrier surface characteristics.

Purpose of the Study:

• To rationally synthesize virus-mimicking nanocarriers with a controlled number of hydrophobic protrusions on a hydrophilic surface.
• To investigate how varying protrusion numbers influence cellular uptake and endo/lysosomal escape.
• To enable efficient drug loading and cytoplasmic delivery.

Main Methods:

• Polystyrene beads coated with porogen-loaded SiO2 shells.
• Controlled porogen removal to induce polymer swelling and create hydrophobic protrusions.
• Characterization of nanocarrier surface properties and protrusion density.
• Assessment of cellular uptake and intracellular trafficking mechanisms.

Main Results:

• Successfully synthesized nanocarriers with up to 175 tunable hydrophobic protrusions.
• Demonstrated that increased protrusion numbers enhance polyvalent interactions with lipid bilayers.
• Showcased enhanced cellular uptake and improved endo/lysosomal escape with increasing protrusions.
• Confirmed efficient drug loading into the nanocarrier cavity via mesopores for cytoplasmic delivery.

Conclusions:

• The developed nanocarriers mimic viral structures for enhanced biological interactions.
• Tunable surface protrusions offer a rational design strategy for advanced nanocarriers.
• This approach facilitates efficient drug delivery to the cytoplasm, maximizing therapeutic potential.