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Figure 3. Structures of BT1718, ICT2588 and Cy-SS-MTX.

ICT2588 was shown to lack the cardiotoxicity of the parent colchicine, achieved through selective targeting
to the tumour . Both of these approaches have significant potential application to OS, given the differential
[78]
expression of MT1-MMP.

Alternative prodrug approaches to selectively deliver MTX have also been considered. For example, Cy-SS-
MTX (see Figure 3), is a glutathione-activated theranostic prodrug consisting of a cystamine functionalised
IR780 (Cy), a near-infrared fluorescent heptamethine dye with tumour targeting properties, conjugated to
MTX. In a co-culture of LO2 (normal hepatocyte) and MCF-7 (breast adenocarcinoma) cells, Cy-SS-MTX
was shown to selectively accumulate within the mitochondria of MCF-7 cells. In addition, in both in vitro
and in vivo models, Cy-SS-MTX was shown to reduce off-target toxicity and improve the anti-tumour
[79]
efficiency of MTX .