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Hemolytic Activity of pH-responsive Polymer-Streptavidin Bioconjugates

Hemolytic Activity of pH-responsive Polymer-Streptavidin Bioconjugates

C A Lackey, N Murthy, O W Press, D A Tirrell, A S Hoffman, P S Stayton

Bioconjug Chem. May-Jun 1999;10(3):401-5.

PMID: 10346870

Abstract:

Drug delivery systems that increase the rate and/or quantity of drug release to the cytoplasm are needed to enhance cytosolic delivery and to circumvent nonproductive cell trafficking routes. We have previously demonstrated that poly(2-ethylacrylic acid) (PEAAc) has pH-dependent hemolytic properties, and more recently, we have found that poly(2-propylacrylic acid) (PPAAc) displays even greater pH-responsive hemolytic activity than PEAAc at the acidic pHs of the early endosome. Thus, these polymers could potentially serve as endosomal releasing agents in immunotoxin therapies. In this paper, we have investigated whether the pH-dependent membrane disruptive activity of PPAAc is retained after binding to a protein. We did this by measuring the hemolytic activity of PPAAc-streptavidin model complexes with different protein to polymer stoichiometries. Biotin was conjugated to amine-terminated PPAAc, which was subsequently bound to streptavidin by biotin complexation. The ability of these samples to disrupt red blood cell membranes was investigated for a range of polymer concentrations, a range of pH values, and two polymer-to-streptavidin ratios of 3:1 and 1:1. The results demonstrate that (a) the PPAAc-streptavidin complex retains the ability to lyse the RBC lipid bilayers at low pHs, such as those existing in endosomes, and (b) the hemolytic ability of the PPAAc-streptavidin complex is similar to that of the free PPAAc.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP138134744	Poly(2-propylacrylic acid)		138134-74-4	Price

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