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Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates

Lackey, Chantal A. and Murthy, Niren and Press, Oliver W. and Tirrell, David A. and Hoffman, Allan S. and Stayton, Patrick S. (1999) Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates. Bioconjugate Chemistry, 10 (3). pp. 401-405. ISSN 1043-1802. doi:10.1021/bc980109k.

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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.

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Tirrell, David A.0000-0003-3175-4596
Additional Information:Copyright © 1999 American Chemical Society. Received September 11, 1998; Revised Manuscript Received March 11, 1999. Publication Date (Web): April 24, 1999. This work was supported by the NIH (NIGMS Grant R01-GM53771-02), the UW Center for Nanotechnology (graduate fellowships to C.A.L. and N.M.), the Office of Technology Transfer at UW, the Washington Technology Center, and the Washington Research Foundation.
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University of WashingtonUNSPECIFIED
Washington Technology CenterUNSPECIFIED
Washington Research FoundationUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:LACbc1999
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Official Citation:Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates Chantal A. Lackey, Niren Murthy, Oliver W. Press, David A. Tirrell, Allan S. Hoffman, and Patrick S. Stayton Bioconjugate Chemistry 1999 10 (3), 401-405
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53385
Deposited By: Anne Hormann
Deposited On:06 Feb 2015 06:02
Last Modified:10 Nov 2021 20:01

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