Reduced drug delivery and penetration, as well as the hypoxic nature of solid tumors compromise drug efficacy. A theranostic agent, referred to as compound 4, has been developed that targets hypoxic solid tumors specifically and elicits anti-tumour effects. Compound 4 is composed of biotin, a nitro group and SN 38. The biotin component directs compound 4 to avidin receptors on solid tumors specifically. The nitro group ensures that compound 4 is activated under the hypoxic conditions of solid tumors, by nitroreductase. Consequently, the activation of compound 4 releases SN 38, a topoisomerase I inhibitor, resulting in a detectable fluorescent signal. The anti-tumor effect of SN 38 is mediated by intercalating into DNA and thereby inhibiting DNA replication. Additionally, SN 38 increases the expression of pro-apoptotic proteins such as FAS, FADD and BID under hypoxic conditions only. Thus, SN 38 demonstrated the ability to penetrate and elicit potent anti-tumor activity in solid tumors.
For further details, please refer to the original paper: Kumar R et al, 2016.