%0 Journal Article
%T Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-¦Á (TNF-¦Á) conjugate for therapeutic application
%A ChuanYun Dai
%A Ya Fu
%A ShaoCheng Chen
%A Biao Li
%A Bo Yao
%A WanHong Liu
%A LiQing Zhu
%A Nan Chen
%A Ji Chen
%A Qiang Zhang
%J Science China Life Sciences
%@ 1869-1889
%D 2013
%I 
%R 10.1007/s11427-012-4431-7
%X To design a releasable PEGylated TNF-¦Á (rPEG-TNF-¦Á), a cathepsin B-sensitive dipeptide (Val-Cit moiety) was inserted into conventional PEG-modified TNF-¦Á (PEG-TNF-¦Á), facilitating its clinical use for anti-tumor therapy. Comparative pharmacokinetic and pharmacodynamic studies showed that the half-lives of both PEGylated forms of TNF-¦Á were ¡«60-fold greater than that of unmodified TNF-¦Á. In addition, the in vitro bioactivity of rPEG-TNF-¦Á was greater than that of PEG-TNF-¦Á with the same degree of PEG modification. Release of TNF-¦Á from rPEG-TNF-¦Á in vitro was dependent on the presence of cathepsin B and was inhibited by a cathepsin B inhibitor. Despite the potent cytotoxicity of unmodified TNF-¦Á against normal cells, its PEGylated forms at higher TNF-¦Á concentrations showed low cytotoxic activity against these cells. In contrast, both forms of PEGylated TNF-¦Á showed potent cytotoxic activity against the B16 and L929 cell lines, with rPEG-TNF-¦Á being 5- and 9-fold more potent, respectively, than PEG-TNF-¦Á. Moreover, rPEG-TNF-¦Á was a more potent in vivo antitumor agent than PEG-TNF-¦Á.
%K tumor necrosis factor-¦Á
%K releasable PEGylation
%K dipeptide
%K anti-tumor effect
%U http://link.springer.com/article/10.1007/s11427-012-4431-7