PAUL LOADMAN,ROBERT FALCONER,JASON GILL,JIANGHONG RAO,HEIKE E. DALDRUP-LINK
申请号：
GB201313900
公开号：
GB2516882A
申请日:
2013.08.02
申请国别(地区):
GB
年份:
2015
代理人:
摘要：
A conjugate comprising a vascular disrupting agent (VDA) which binds to the colechicine binding site of tubulin, a matrix metalloprotease (MMP) cleavable linker comprising the amino acid sequence gly-hof-tyr-leu- or arg-ser-cit-gyl-hof-tyr-, a nanoparticle bearing a magnetic resonance imaging (MRI) contrast agent, and wherein the conjugate doe not comprise folate. These nanoparticles are targeted to tumour sites, which may have specific elevated MMP- 14 activity which cleaves the linker. This single conjugate to simultaneously deliver a vascular disrupting agent (VDA) and a MRI contrast agent to a tumour site. The VDA may be a colchicines, anlagog, combrestatin, phenstatin, podophyllotoxin, steganacin, amphethinile or stilbene. Consequently, the present invention provides a cancer "theranostic" which improves therapeutic efficacy whilst simultaneously reducing dose-limiting systemic toxicities and provides a tool for rapidly and non-invasively identifying tumour location, monitoring drug delivery and pharmacodynamics.
