Hemolytic activity of pH-responsive polymer-streptavidin bioconjugates

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Cell Biology

Background:

• Drug delivery systems require enhanced cytosolic delivery to improve efficacy.
• Poly(2-ethylacrylic acid) (PEAAc) and poly(2-propylacrylic acid) (PPAAc) exhibit pH-dependent hemolytic properties.
• PPAAc shows greater pH-responsive hemolytic activity than PEAAc at endosomal pH.

Purpose of the Study:

• To investigate if PPAAc retains its pH-dependent membrane-disrupting activity after binding to a protein.
• To evaluate PPAAc-streptavidin complexes as potential endosomal releasing agents for immunotoxin therapies.

Main Methods:

• Synthesized PPAAc-streptavidin complexes by conjugating biotin to PPAAc and then binding to streptavidin.
• Measured the hemolytic activity of these complexes across various polymer concentrations, pH values, and polymer-to-streptavidin ratios (3:1 and 1:1).
• Assessed the ability of the complexes to disrupt red blood cell (RBC) membranes.

Main Results:

• The PPAAc-streptavidin complex maintained its ability to lyse RBC lipid bilayers at acidic pHs, mimicking endosomal conditions.
• The hemolytic activity of the PPAAc-streptavidin complex was comparable to that of free PPAAc.
• The membrane-disrupting activity was observed at low pH values relevant to endosomal escape.

Conclusions:

• PPAAc-streptavidin complexes retain pH-dependent membrane lytic activity.
• These complexes show potential as endosomal releasing agents in drug delivery and immunotoxin therapies.
• The polymer's activity is preserved upon complexation with streptavidin, suggesting utility in targeted delivery systems.