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Oncol Lett. 2015 Mar;9(3):1337-1342. Epub 2014 Dec 29.

Chlorotoxin-conjugated onconase as a potential anti-glioma drug.

Author information

1
Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai 200092, P.R. China.

Abstract

Gliomas are rarely curable malignant brain tumors arising from normal glial cells. The scorpion-derived small peptide, chlorotoxin (CTX), can selectively bind malignant gliomas. In the present study, a CTX-conjugated onconase (Onc), a small cytotoxic ribonuclease, was prepared as a potential anti-glioma drug. In this conjugate, recombinant CTX was covalently linked with recombinant Onc by reversible disulfide linkage. The chemically conjugated CTX-Onc showed much higher cytotoxicity to the cultured glioma U251 and SHG-44 cells than the physical mixture of CTX and Onc (CTX + Onc). In the nude mouse models bearing subcutaneous U251 or SHG-44 tumors, the CTX-Onc conjugate also showed improved anti-tumor effects than the CTX + Onc control. These results suggested that the reversible chemical-conjugated CTX promoted the tumor targeting of Onc, and thus the present CTX-Onc conjugate could be further developed as a potential targeted anti-glioma drug.

KEYWORDS:

chemical conjugation; chlorotoxin; glioma; onconase; targeted therapy

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