Light Control of Protein Solubility Through Isoelectric Point Modulation

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Engineering

Background:

• Photoactivated depot (PAD) approaches control protein release using light-induced solubility changes.
• Traditional polymer-based PAD systems face challenges with material inefficiency and polymer clearance.

Purpose of the Study:

• To develop polymer-free photoactivated depots for therapeutic protein release.
• To create insulin depots controlled by light-induced isoelectric point and solubility shifts.

Main Methods:

• Linking basic groups to insulin via a light-cleaved linker to alter its isoelectric point (pI).
• Synthesizing and characterizing modified insulins with shifted pI values.
• Evaluating depot formation, protein release kinetics, and material clearance in vitro.

Main Results:

• Four modified insulins were synthesized with shifted pI values, enabling precipitation at physiological pH.
• P2-insulin demonstrated solubility at pH 4 and precipitation at pH 7.2.
• Irradiation released native, soluble insulin in a first-order kinetic manner, leaving behind small, absorbable molecules.

Conclusions:

• Polymer-free photoactivated depots for insulin release were successfully developed.
• The approach utilizes light-induced pI shifts to control protein solubility and depot formation.
• These materials offer an improved, efficient, and potentially ideal platform for photoactivated therapeutic delivery.