Entropy-Driven Quick Loading of Functional Proteins in Nanohydrogels for Highly Efficient Tumor Targeting Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Understanding tumor development drives the need for advanced nanodrug delivery systems.
• Proteins are crucial carriers in nanodrugs to prevent immune system clearance and ensure targeted delivery.
• Existing methods face challenges in efficient protein loading and targeted delivery of nanotherapeutics.

Purpose of the Study:

• To develop a universal and efficient strategy for preparing protein-functionalized targeting nanodrugs.
• To investigate the loading efficiency, protein activity retention, and targeting capability of the novel nanodrug system.
• To evaluate the anti-tumor efficacy of the targeted nanodrug for potential clinical applications.

Main Methods:

• Proteins (albumin, horseradish, transferrin, ricin) were rapidly loaded into polyacrylic acid nanohydrogels (PAA-NGs) via an entropy-driven process.
• Targeting agents were oriented onto the nanocarrier surface using a facile technique.
• The anti-tumor protein ricin and transferrin (Tf) were loaded, forming PAA-BB@Ricin/Tf, and its efficacy was tested.

Main Results:

• High loading efficiency (99%) and loading content (approx. 50%) were achieved for various proteins within 1 minute.
• The activity of the loaded proteins was well-retained after release.
• The oriented targeting system demonstrated significantly enhanced tumor cell uptake and targeting effect compared to non-oriented systems, leading to remarkable anti-tumor activity.

Conclusions:

• A new universal strategy for protein delivery and targeting in nanodrugs has been successfully developed.
• The protein-loaded nanodrugs exhibit excellent loading characteristics, protein activity retention, and targeted delivery capabilities.
• This approach holds significant potential for improving nanodelivery systems and advancing individualized tumor treatment in clinical settings.