Papers Published

  1. D. Y. Furgeson and M. R. Dreher and A. Chilkoti, Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors, Journal Of Controlled Release, vol. 110 no. 2 (January, 2006), pp. 362 -- 369 .
    (last updated on 2009/09/02)

    A thermoresponsive, genetically engineered, elastin-like polypeptide (ELP) containing a C-terminal cysteine residue was synthesized and purified by inverse transition cycling (ITC) and conjugated to doxorubicin (Dox) molecules through four different pH-sensitive, maleimide-activated, hydrazone linkers. The efficiency of Dox activation, conjugation ratios to ELP and biophysical characterization-hydrodynamic radius (R-h) and the temperature transition kinetics-of the ELP-Dox conjugates and pH-mediated release of Dox were quantified in this study. Conjugation ratios of the maleimide-activated Dox to the thiol group of a unique cysteine in the ELP were close to unity. The R-h of the conjugate increased as the linker length between the ELP backbone and Dox was increased. The linker structure and length had little effect on the T-t of the ELP-Dox conjugates, as all conjugates exhibited T-t's that were similar to the native ELP. However, the ELP-Dox conjugates with longer linkers exhibited slower transition kinetics compared to the ELP-Dox conjugates with shorter linkers. The highest release of the ELP-Dox conjugate by cleavage of the hydrazone bond at pH 4 was nearly 80\% over 72 h and was exhibited by the conjugate with the shortest linker. (c) 2005 Elsevier B.V. All rights reserved.