Protein Nanogels with Temperature-Induced Reversible Structures and Redox Responsiveness

Area of Science:

• Materials Science
• Biotechnology
• Polymer Chemistry

Background:

• Natural smart structures exhibit stimulus-responsive changes in conformation and function.
• Designing synthetic materials with adaptable structures and functionalities is crucial for advanced applications.
• Protein nanogels offer a promising platform for biomimetic material development.

Purpose of the Study:

• To synthesize virus-mimicking protein nanogels with temperature-induced reversible structures and redox responsiveness.
• To investigate the control over nanogel properties like lower critical solution temperature (LCST) and size.
• To evaluate the potential of these nanogels for protein delivery.

Main Methods:

• Synthesis of protein nanogels via thiol-disulfide exchange reaction between a thermally responsive polymer and bovine serum albumin (BSA).
• Characterization of nanogel structural changes in response to temperature variations (below and above LCST).
• Assessment of nanogel dissociation using glutathione and evaluation of *in vitro* cytotoxicity and cell uptake.

Main Results:

• Successfully synthesized protein nanogels exhibiting reversible structural changes with temperature.
• Demonstrated control over nanogel LCST and size by adjusting reaction conditions.
• Observed temperature-dependent structural transitions: BSA embedded below LCST, BSA at shells above LCST.
• Confirmed nanogel dissociation in the presence of glutathione.
• *In vitro* assays showed low cytotoxicity towards 3T3, 293T, and MCF-7 cells.
• Confirmed internalization of nanogels into MCF-7 cells.

Conclusions:

• The synthesized protein nanogels mimic natural smart structures with tunable, temperature-responsive properties.
• These nanogels exhibit controlled structural changes and redox-triggered dissociation.
• The low toxicity and cellular uptake suggest significant potential for protein delivery applications.