Enhancement of anti-tumor activity of hybrid peptide in conjugation with carboxymethyl dextran via disulfide linkers.
作者： Arong Gaowa , Tomohisa Horibe , Masayuki Kohno , Yasuhiko Tabata , Hiroshi Harada
DOI: 10.1016/J.EJPB.2015.03.015
关键词: Drug delivery 、 Peptide 、 Cysteine 、 Conjugate 、 Biochemistry 、 Chemistry 、 Drug carrier 、 Dextran 、 In vivo 、 Glutathione
摘要: To improve the anti-tumor activity of EGFR2R-lytic hybrid peptide, we prepared peptide-modified dextran conjugates with disulfide bonds between thiolated carboxymethyl (CMD-Cys) and cysteine-conjugated peptide (EGFR2R-lytic-Cys). In vitro release studies showed that was released from CMD-s-s-peptide conjugate in a concentration-dependent manner presence glutathione (GSH, 2μM-2mM). The exhibited similar cytotoxic free alone against human pancreatic cancer BxPC-3 cells vitro. Furthermore, it shown were highly accumulated tumor tissue mouse xenograft model using cells, more effective than peptide. addition, plasma concentrations moderately increased elimination half-life prolonged after intravenous injection conjugates. These results demonstrated based on CMD polymer would be potentially useful carriers for sustained vivo.
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